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Chen C, Xu SJ, Zhang ZF, You CX, Luo YF, Chen RQ, Chen SC. Severe postoperative complications after minimally invasive esophagectomy reduce the long-term prognosis of well-immunonutrition patients with locally advanced esophageal squamous cell carcinoma. Ann Med 2025; 57:2440622. [PMID: 39673205 DOI: 10.1080/07853890.2024.2440622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 12/16/2024] Open
Abstract
BACKGROUND While severe postoperative complications (SPCs) impact cancer prognosis, their effect on locally advanced esophageal squamous cell carcinoma (ESCC) patients with varying immunonutritional statuses after minimally invasive esophagectomy (MIE) is unclear. METHODS This retrospective study analyzed 442 patients with locally advanced ESCC who underwent MIE, investigating the relationship between SPCs and survival based on preoperative immunonutritional status, determined by the prognostic nutritional index (PNI). Nomograms were developed for patients with preserved immunonutritional status using Cox regression, and their performance was assessed. RESULTS Of the patients, 102 (23.1%) experienced SPCs after MIE. Five-year overall survival (OS) and disease-free survival (DFS) were significantly different between SPCs and non-SPCs groups (p < 0.001). In the preserved immunonutritional group, SPCs significantly reduced 5-year OS (p = 0.008) and DFS (p = 0.011), but not in the poor immunonutritional group (OS p = 0.152, DFS p = 0.098). Multivariate Cox regression identified SPCs as an independent risk factor for OS (HR = 1.653, p = 0.013) and DFS (HR = 1.476, p = 0.039). A nomogram for predicting OS and DFS in preserved immunonutritional patients demonstrated excellent performance. CONCLUSIONS SPCs significantly affect prognosis in ESCC patients with preserved immunonutritional status after MIE. Nomograms based on SPCs can predict OS and DFS in these patients.
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Affiliation(s)
- Chao Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Shao-Jun Xu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Zhi-Fan Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Cheng-Xiong You
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Yun-Fan Luo
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Rui-Qin Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Shu-Chen Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian Province, China
- Fujian Provincial Key Laboratory of Cardiothoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
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Baba Y, Tajima K, Yoshimura K. Intestinal and esophageal microbiota in esophageal cancer development and treatment. Gut Microbes 2025; 17:2505118. [PMID: 40376843 PMCID: PMC12087659 DOI: 10.1080/19490976.2025.2505118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 03/03/2025] [Accepted: 05/07/2025] [Indexed: 05/18/2025] Open
Abstract
Esophageal cancer (EC) is the eleventh most commonly diagnosed cancer, and its prognosis remains poor. Several challenges remain for improving the clinical outcomes of EC, and improving technologies for early detection, diversifying treatment options, and advancing personalized treatment are essential. Alterations in the intestinal and esophageal microbiota are associated with the pathogenesis and progression of EC; for instance, Fusobacterium nucleatum is important in the pathogenesis and progression of esophageal squamous cell carcinoma. Therefore, a novel diagnostic biomarker may be identified using the intestinal microbiota. Furthermore, targeting the intestinal and esophageal microbiota may help in the early detection of EC, use of a novel prognostic biomarker, and even the detection of a therapeutic target, resulting in a more individualized therapeutic approach for EC. In this review, we summarize the clinical research focused on the intestinal and esophageal microbiota in EC development and its treatment, and discuss the challenges in the clinical application of intestinal and esophageal microbiota.
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Affiliation(s)
- Yuta Baba
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan
- Division of Hematology, Department of Medicine, Showa Medical University Fujigaoka Hospital, Kanagawa, Japan
| | - Kohei Tajima
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan
- Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
| | - Kiyoshi Yoshimura
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan
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Liu W, Zhang J, Wu M, Ren D, Chen C, Du Z, Li Q, Chang J, Pu Q, Liu Z. Ponicidin triggered ferroptosis in esophageal squamous cell carcinoma by suppressing the SLC7A11/Glutathione/GPX4 signalling axis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 143:156925. [PMID: 40456202 DOI: 10.1016/j.phymed.2025.156925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 05/17/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND Ponicidin, a diterpenoid derived from Rabdosia rubescens, exhibits potent antitumor activity. However, its mechanisms against esophageal squamous cell carcinoma (ESCC) remain obscure. This study aims to explore the effects of ponicidin against ESCC and reveal its molecular mechanisms. METHODS The anti-ESCC effects of ponicidin were evaluated using CCK-8 assay, colony formation and transwell invasion assays. Cell cycle progression and mitochondrial membrane potential were analyzed using flow cytometry. Proteomics was applied to explore ponicidin's mechanisms. Ferroptosis induction was evaluated by quantifying reactive oxygen species, Fe2+, malondialdehyde, glutathione, and lipid peroxidation levels. Docking and molecular dynamics simulations were conducted to identify the targets. siRNA was employed to validate target. The efficacy of ponicidin on tumorigenicity was explored in tumor xenograft mouse models, and its biosafety was evaluated via hemolysis assays, plasma ALT, AST, BUN, and CRE levels, as well as histopathological examinations. Western blot was used to analyze protein expression levels. RESULTS Ponicidin inhibited ESCC cell proliferation, arrested cells in the G2/M phase, reduced mitochondrial membrane potential, and suppressed tumor growth without evident toxicity. Proteomics identified that ponicidin-induced ferroptosis is the predominant mechanism against ESCC. Ponicidin increased reactive oxygen species, malondialdehyde, Fe2+, lipid peroxidation and glutathione depletion. Ferrostatin-1 pretreatment reduced lipid peroxidation, rescued PON induced inhibition of cell viability, and reversed the decreased expression of SLC7A11, GPX4 and GSR. Molecular docking revealed strong binding affinity of PON to GPX4 (-7.31±0.55 kcal/mol) and SLC7A11 (-8.19±0.37 kcal/mol). Molecular dynamics simulations confirmed stabilized complexes with total interaction energies of -23.43 ± 2.13 kcal/mol (GPX4-PON) and -31.42 ± 0.84 kcal/mol (SLC7A11-PON). siRNA-mediated knockdown of GPX4 and SLC7A11 reduced ESCC sensitivity to ponicidin-induced ferroptosis. CONCLUSION This study provides the first evidence that ponicidin triggers ferroptosis in ESCC cells via suppression of the SLC7A11/glutathione/GPX4 signalling axis, offering actionable targets for ferroptosis-enhancing combination therapies.
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Affiliation(s)
- Wenhu Liu
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China.
| | - Jinhua Zhang
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China; Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, 637100, China
| | - Min Wu
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China; Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, 637100, China
| | - Dan Ren
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China; Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, 637100, China
| | - Chuan Chen
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China
| | - Zuo Du
- School of Public Health, North Sichuan Medical College, Nanchong, 637100, China
| | - Qianhui Li
- School of Pharmacy, North Sichuan Medical College, Nanchong, 637100, China
| | - Jinxia Chang
- School of Basic Medical Sciences & Forensic Medical, North Sichuan Medical College, Nanchong, 637100, China
| | - Qi Pu
- Technology Innovation Center, Chong Qing Medical University, Chongqing, 400016, China
| | - Zhenzhong Liu
- School of Public Health, North Sichuan Medical College, Nanchong, 637100, China.
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Nakai S, Makino T, Momose K, Yamashita K, Tanaka K, Miyata H, Yamamoto S, Motoori M, Kimura Y, Kawabata R, Hirao M, Matsuyama J, Akamaru Y, Morihara H, Ueyama A, Kurokawa Y, Morii E, Wada H, Eguchi H, Doki Y. Exploring predictive biomarkers of efficacy and survival with nivolumab treatment for unresectable/recurrent esophageal squamous cell carcinoma. Esophagus 2025; 22:360-372. [PMID: 40274705 DOI: 10.1007/s10388-025-01120-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 03/11/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Programmed cell death protein-1 (PD-1) blockade has improved survival for patients with esophageal squamous cell carcinoma (ESCC), but response rates are low. Biomarkers to predict who will benefit from PD-1 blockade are urgently needed. METHODS This multicenter study involved 250 patients with recurrent/unresectable advanced ESCC receiving nivolumab as second- or later-line therapy. We assessed tumor-infiltrating T lymphocytes (TILs) and tertiary lymphoid structure (TLS) density using immunohistochemistry and hematoxylin/eosin staining in surgical specimens and pre-nivolumab endoscopic biopsies. RESULTS In surgical specimens, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ lymphocyte count (160 vs. 95.2 cells/field, P = 0.0494), CD8/Foxp3 ratio (6.52 vs. 2.72, P = 0.0053), and TLS density (0.21/mm2 vs. 0.10/mm2, P = 0.0005). In terms of overall survival, multivariate analysis identified CD8/Foxp3 ratio (hazard ratio [HR] = 1.83, P = 0.0050) and TLS density (HR = 1.67, P = 0.0171 as independent prognostic parameters in surgical specimens. Similarly, in endoscopic biopsies, clinical response (vs. non-response) to nivolumab correlated significantly with CD8+ counts (254 cells/mm2 vs. 124 cells/mm2, P = 0.0344), CCR8+ lymphocyte count (62.6 cells/mm2 vs. 140 cells/mm2, P = 0.0355), CD8/Foxp3 ratio (2.09 vs. 0.89, P = 0.040), and CD8/CCR8 ratio (2.34 vs. 0.89, P = 0.0020). Multivariate analysis also identified CD8/CCR8 ratio in endoscopic biopsies (HR = 1.66, P = 0.0313) as an independent prognostic parameter. CONCLUSIONS CD8+ and CCR8+ cell counts, CD8/Foxp3 and CD8/CCR8 ratios, and TLS density may be predictive biomarkers of therapeutic efficacy and survival with PD-1 blockade for ESCC.
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Affiliation(s)
- Shigeto Nakai
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
| | - Kota Momose
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Kotaro Yamashita
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Masaaki Motoori
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
| | - Yutaka Kimura
- Department of Gastroenterological Surgery, Kindai University Nara Hospital, Nara, Japan
| | - Ryohei Kawabata
- Department of Surgery, Sakai City Medical Center, Osaka, Japan
| | - Motohiro Hirao
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Jin Matsuyama
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, Osaka, Japan
| | - Yusuke Akamaru
- Department of Surgery, Osaka Rosai Hospital, Osaka, Japan
| | - Hitomi Morihara
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Azumi Ueyama
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
- Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan
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Shao K, Du Y, Xu L, Jiang Y, Chen Q, Zeng J, Cai L, Xu Y, Sun X, Mao W, Wang C. Outcomes of neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. Surgery 2025; 183:109383. [PMID: 40319526 DOI: 10.1016/j.surg.2025.109383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 03/25/2025] [Accepted: 03/31/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND Esophageal squamous carcinoma is a prevalent cancer worldwide, particularly in China. Few studies have compared the treatment effects of neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy on the long-term prognosis of patients with esophageal squamous carcinoma. This study analyzed the 3-year overall survival rate of patients with locally advanced esophageal squamous carcinoma treated with esophagectomy after neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy. METHODS A total of 309 patients with esophageal squamous carcinoma who underwent neoadjuvant chemoradiotherapy between 2010 and 2020 and 88 who underwent neoadjuvant immunochemotherapy between 2019 and 2020 at Zhejiang Cancer Hospital were included in this study. Propensity score matching with a 1:1 ratio and a caliper of 0.02 was used to balance the baseline characteristics. RESULTS The study included 397 patients with locally advanced thoracic segmental esophageal squamous carcinoma, including 88 who received neoadjuvant immunochemotherapy and 309 who received neoadjuvant chemoradiotherapy. After propensity score matching, there were no significant differences in pathologic complete response between the 2 groups (21.3% vs 33.3%, χ2 = 2.148, P = .143), and the neoadjuvant immunochemotherapy group demonstrated a greater 3-year overall survival rate (73.8% vs 54.8%, P = .003), particularly for patients with a primary stage Ⅲ diagnosis (T3N1M0, T1-3N2M0) or an initial suspicion of lymph node metastases. Pathologic complete response emerged as a reliable predictor of long-term outcomes in patients receiving neoadjuvant chemoradiotherapy, but not in those receiving neoadjuvant immunochemotherapy. CONCLUSION Neoadjuvant immunochemotherapy was associated with improved long-term prognosis in patients with a primary stage Ⅲ diagnosis or an initial suspicion of lymph node metastases. Neoadjuvant immunochemotherapy plus surgery emerged as an effective therapeutic strategy for treating locally advanced thoracic segmental esophageal squamous carcinoma.
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Affiliation(s)
- Kelong Shao
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China; Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Yening Du
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China; The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Liwei Xu
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Youhua Jiang
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Qixun Chen
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Jian Zeng
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Lei Cai
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Yujin Xu
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xiaojiang Sun
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, China
| | - Weimin Mao
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China; Zhejiang Provincial Key Laboratory of Thoracic Tumour Diagnosis and Treatment Technology Research, Hangzhou, China
| | - Changchun Wang
- Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou, China; Zhejiang Provincial Key Laboratory of Thoracic Tumour Diagnosis and Treatment Technology Research, Hangzhou, China.
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He G, Wu Z, Yang X, Luo X, Zhang L, Du Z, Li S, Wan C. Design and synthesis of thiolutin derived PSMD14/HDAC dual-target inhibitors against esophageal squamous cell carcinoma. Bioorg Chem 2025; 161:108500. [PMID: 40311241 DOI: 10.1016/j.bioorg.2025.108500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/17/2025] [Accepted: 04/20/2025] [Indexed: 05/03/2025]
Abstract
Esophageal cancer is one of the most migratory, invasive, and lethal malignancies and has a poor prognosis, highlighting the urgent need to develop more effective drugs for its treatment. Given that PSMD14 and HDAC play an important role in the treatment of esophageal cancer, thiolutin is used as a lead compound to design and synthesize a series of dual-target PSMD14/HDAC small molecule inhibitors, aiming to discover more effective anti-esophageal cancer drugs. Through the in vitro screening of PSMD14/HDAC enzyme inhibitory activities of a series of thiolutin derivatives, it was found that compound 8b, with a linker length of 8 and a Zn2+-chelating group of 1,2-phenylenediamine, exhibited the most balanced inhibitory activity against PSMD14/HDAC.The impact of 8b on PSMD14/HDAC at the cellular level was evaluated, and its drug-like properties were further assessed in vivo. Compound 8b demonstrates balanced dual-target activity (PSMD14 IC50 = 238.7 ± 27 nM, HDAC1 IC50 = 141.2 ± 10.3 nM) and excellent cytotoxicity against esophageal cancer cells (IC50 = 30-250 nM), effectively reversing epithelial-mesenchymal transition in cancer cells. Moreover, 8b exhibited excellent pharmacokinetic characteristics. More importantly, in a nude mouse xenograft model with subcutaneous transplantation of KYSE 30 cells, compound 8b (0.8 mg/kg, BID, PO, TGI = 81 %; 0.8 mg/kg, Q3D, SC, TGI = 77 %) significantly inhibited tumor growth, outperforming single-agent or combination treatments, thereby highlighting the therapeutic advantages of dual-target inhibition. These findings highlight the potential of dual-target PSMD14/HDAC inhibitors as a promising strategy for developing anti-esophageal cancer drugs.
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Affiliation(s)
- Guoguo He
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China
| | - Zhenhui Wu
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China
| | - Xuan Yang
- College of Chemical Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Xinrong Luo
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China
| | - Lili Zhang
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China
| | - Zhenting Du
- College of Chemical Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Shuwei Li
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China.
| | - Chuanxing Wan
- Key Laboratory of Conservation and Utilization of Biological Resources in the Tarim Basin, Alaer, Xinjiang 843300, PR China; College of Life Science and Technology, Tarim University, Alaer, Xinjiang 843300, PR China.
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Massaro G, Paulet A, Lavacchi D, Brugia M, Rossini D, Giommoni E, Catalano M, Pillozzi S, Antonuzzo L, Roviello G. Immune checkpoint inhibitors in the first-line treatment of esophageal squamous cell carcinoma: Minireview for a big shift. World J Gastrointest Oncol 2025; 17:106707. [DOI: 10.4251/wjgo.v17.i6.106707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/09/2025] [Accepted: 04/23/2025] [Indexed: 06/13/2025] Open
Abstract
Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages, with esophageal squamous cell carcinoma being the predominant subtype worldwide. Standard first-line chemotherapy provides limited survival benefits, with a median overall survival of less than 1 year. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have transformed the treatment landscape, improving overall survival and progression-free survival. However, response rates remain variable, with programmed death ligand 1 (PD-L1) expression being the primary predictive biomarker. The variability in PD-L1 testing methods and immune microenvironment alterations after prior treatments complicate patient selection for ICIs. Several phase 3 trials, including KEYNOTE-590 and CheckMate 648, have demonstrated the efficacy of ICIs combined with chemotherapy, particularly in patients positive for PD-L1. Despite these advances, long-term survival remains low, emphasizing the need for better biomarkers and novel therapeutic strategies. This review explored current first-line treatment options for esophageal squamous cell carcinoma, challenges in biomarker-based patient selection, and emerging therapeutic approaches.
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Affiliation(s)
- Giulia Massaro
- School of Human Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
| | - Alexandra Paulet
- School of Human Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
| | - Daniele Lavacchi
- Oncology Unit, Careggi University Hospital, Florence 50134, Tuscany, Italy
| | - Marco Brugia
- Oncology Unit, Azienda Universitaria Ospedaliera Careggi, Florence 50134, Tuscany, Italy
| | - Daniele Rossini
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
| | - Elisa Giommoni
- Oncology Unit, Azienda Universitaria Ospedaliera Careggi, Florence 50134, Tuscany, Italy
| | - Martina Catalano
- Department of Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
| | - Serena Pillozzi
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
| | - Lorenzo Antonuzzo
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Tuscany, Italy
| | - Giandomenico Roviello
- Department of Health Sciences, University of Florence, Florence 50134, Tuscany, Italy
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8
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Zhang SK, Jiang L, Jiang CL, Cao Q, Chen YQ, Chi H. Unveiling genetic susceptibility in esophageal squamous cell carcinoma and revolutionizing pancreatic cancer diagnosis through imaging. World J Gastrointest Oncol 2025; 17:102544. [DOI: 10.4251/wjgo.v17.i6.102544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 02/16/2025] [Accepted: 04/14/2025] [Indexed: 06/13/2025] Open
Abstract
Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management. Lin et al identified activin A receptor type 1C polymorphisms (rs4556933/rs77886248) as esophageal squamous cell carcinoma risk modifiers in Chinese Han populations through a case-control study (1264 patients/1361 controls), revealing transforming growth factor-beta pathway-mediated susceptibility in older male smokers (P < 0.001). Concurrently, Luo et al established imaging-based differentiation of pancreatic cancer subtypes (pancreatic ductal adenocarcinoma vs neuroendocrine tumors) via retrospective analysis of 500 cases (area under the curve = 0.89), enabling earlier intervention. These findings underscore the transformative potential of combining genetic risk stratification with advanced imaging to guide precision screening and therapeutic strategies, addressing critical gaps in esophageal and pancreatic cancer outcomes.
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Affiliation(s)
- Sheng-Ke Zhang
- Clinical Medical College, Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Lai Jiang
- Clinical Medical College, Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Cheng-Lu Jiang
- Clinical Medical College, Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Qiang Cao
- School of Medicine, Macau University of Science and Technology, Macau 999078, China
| | - Yu-Quan Chen
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria 3004, Australia
| | - Hao Chi
- Clinical Medical College, Southwest Medical University, Luzhou 646000, Sichuan Province, China
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Fang C, Wu L, Yang X, Xie K, Zhang P, Feng Y, Ma H, Tong X. Decursin Suppresses Esophageal Squamous Cell Carcinoma Progression via Orchestrated Cell Cycle Deceleration, Apoptotic Activation, and Oncoprotein Degradation. Int J Mol Sci 2025; 26:5391. [PMID: 40508204 PMCID: PMC12154389 DOI: 10.3390/ijms26115391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 06/01/2025] [Accepted: 06/03/2025] [Indexed: 06/16/2025] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with limited therapeutic options. This study investigated the antitumor efficacy and mechanisms of decursin, a natural pyranocoumarin derivative, against ESCC. In vitro analyses demonstrated that decursin selectively inhibited ESCC cell viability (IC50: 14.62 ± 0.61-26.20 ± 2.11 μM across TE-1, KYSE-30, and KYSE-150 cell lines) without affecting normal esophageal epithelial cells (Het-1A). Decursin (10 μM) suppressed colony formation, impaired wound healing (p < 0.001 at 48 h), and reduced Transwell migration/invasion in KYSE-150 cells. Subcutaneous xenograft models revealed significant tumor growth inhibition (p < 0.01) with decursin treatment (10 mg/kg, intraperitoneal), accompanied by no systemic toxicity. Mechanistically, decursin induced G0/G1 cell cycle deceleration (p < 0.01) and apoptosis through ubiquitin-proteasome-mediated degradation of oncoproteins TP63 and SOX2. Time- and dose-dependent protein suppression was reversed by proteasome inhibitor MG-132, but unaffected by lysosomal inhibition. These findings establish decursin as a promising therapeutic agent for ESCC, functioning via proteasomal degradation of key oncogenic drivers, and provide a rationale for decursin's further development as a targeted monotherapy or chemosensitizer in multimodal regimens.
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Affiliation(s)
- Chen Fang
- Department of Thoracic and Cardiovascular Surgery, Medical Center of Soochow University, Suzhou 215000, China; (C.F.); (L.W.); (X.Y.); (K.X.)
- Advanced Molecular Pathology Institute of Soochow University and SANO, Suzhou 215128, China;
| | - Lin Wu
- Department of Thoracic and Cardiovascular Surgery, Medical Center of Soochow University, Suzhou 215000, China; (C.F.); (L.W.); (X.Y.); (K.X.)
- Advanced Molecular Pathology Institute of Soochow University and SANO, Suzhou 215128, China;
| | - Xiangzhe Yang
- Department of Thoracic and Cardiovascular Surgery, Medical Center of Soochow University, Suzhou 215000, China; (C.F.); (L.W.); (X.Y.); (K.X.)
- Advanced Molecular Pathology Institute of Soochow University and SANO, Suzhou 215128, China;
| | - Kai Xie
- Department of Thoracic and Cardiovascular Surgery, Medical Center of Soochow University, Suzhou 215000, China; (C.F.); (L.W.); (X.Y.); (K.X.)
| | - Peng Zhang
- Advanced Molecular Pathology Institute of Soochow University and SANO, Suzhou 215128, China;
| | - Yu Feng
- Department of Thoracic Surgery, The First Clinical Medical College of Soochow University, Suzhou 215006, China;
| | - Haitao Ma
- Department of Thoracic and Cardiovascular Surgery, Medical Center of Soochow University, Suzhou 215000, China; (C.F.); (L.W.); (X.Y.); (K.X.)
- Department of Thoracic Surgery, The First Clinical Medical College of Soochow University, Suzhou 215006, China;
| | - Xing Tong
- Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
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Fan H, Liu J, Hu X, Cai J, Su B, Jiang J. The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development. Apoptosis 2025; 30:1202-1215. [PMID: 40146486 DOI: 10.1007/s10495-025-02101-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2025] [Indexed: 03/28/2025]
Abstract
X-linked inhibitor of apoptosis protein (XIAP) is the most potent endogenous member of the inhibitor of apoptosis protein family. XIAP exerts its anti-apoptotic effects by inhibiting both the death receptor pathway and mitochondrial pathway of apoptosis through various mechanisms such as directly binding to caspases, activating the nuclear factor kappa B (NF-κB) pathway, and other signaling pathways. These processes are closely related to tumor development and progression, making XIAP a therapeutic target for various types of cancer. This article will first review the structural characteristics and biological functions of XIAP, followed by its effects on tumors and an overview of XIAP-targeted inhibitors.
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Affiliation(s)
- Hui Fan
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jiyuan Liu
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xiangyan Hu
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jiye Cai
- Department of Chemistry, Jinan University, Guangzhou, 510632, China
| | - Bo Su
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jinhuan Jiang
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
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11
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Chan WC, Millwood I, Kartsonaki C, Du H, Schmidt D, Stevens R, Chen J, Pei P, Yu C, Sun D, Lv J, Han X, Li L, Chen Z, Yang L, for the China Kadoorie Biobank (CKB) Collaborative Group. Adiposity and risks of gastrointestinal cancers: A 10-year prospective study of 0.5 million Chinese adults. Int J Cancer 2025; 156:2094-2106. [PMID: 39737804 PMCID: PMC11970548 DOI: 10.1002/ijc.35303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 10/17/2024] [Accepted: 10/29/2024] [Indexed: 01/01/2025]
Abstract
Associations of adiposity with risks of oesophageal squamous cell carcinoma (ESCC) and non-cardia stomach cancer, both prevalent in China, are still inconclusive. While adiposity is an established risk factor for colorectal cancer, the relevance of fat-free mass and early-adulthood adiposity remains to be explored. The prospective China Kadoorie Biobank study included 0.5 million adults (aged 30-79 years) from 10 areas in China. Participants' body size and composition were measured at baseline and at resurveys (amongst a subset). After >10 years of follow-up, 2350, 3345 and 3059 incident cases of oesophageal (EC), stomach (SC) and colorectal (CRC) cancers were recorded, respectively. Cox regression was used to estimate hazard ratios (HRs) for these cancers in relation to different adiposity traits. General and central adiposity were inversely associated with EC (primarily ESCC) risk, with HRs of 0.81 (95% CI 0.77-0.85), 0.76 (0.72-0.81) and 0.87 (0.83-0.92) per SD increase in usual levels of BMI, body fat percentage (BF%) and waist circumference (WC), respectively. Adiposity was also inversely associated with SC risk [HR = 0.79 (0.75-0.83) and 0.88 (0.84-0.92) per SD increase in usual BF% and WC], with heterogeneity by cardia and non-cardia subsites, and positively associated with CRC [HR = 1.09 (1.03-1.15) and 1.17 (1.12-1.22) per SD higher usual BF% and WC]. Fat-free mass was inversely associated with EC [HR = 0.93 (0.89-0.98) per SD increase] but positively associated with CRC [1.09 (1.04-1.14)], while BMI at age 25 was positively associated with all three cancers. After mutual adjustment, general adiposity remained inversely associated with EC and SC, while central adiposity remained positively associated with CRC.
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Affiliation(s)
- Wing Ching Chan
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Iona Millwood
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Christiana Kartsonaki
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Huaidong Du
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Daniel Schmidt
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Rebecca Stevens
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Junshi Chen
- China National Center For Food Safety Risk AssessmentBeijingChina
| | - Pei Pei
- Peking University Center for Public Health and Epidemic Preparedness & ResponseBeijingChina
| | - Canqing Yu
- Peking University Center for Public Health and Epidemic Preparedness & ResponseBeijingChina
- Department of Epidemiology and Biostatistics, School of Public HealthPeking University Health Science CenterBeijingChina
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationBeijingChina
| | - Dianjianyi Sun
- Peking University Center for Public Health and Epidemic Preparedness & ResponseBeijingChina
- Department of Epidemiology and Biostatistics, School of Public HealthPeking University Health Science CenterBeijingChina
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationBeijingChina
| | - Jun Lv
- Peking University Center for Public Health and Epidemic Preparedness & ResponseBeijingChina
- Department of Epidemiology and Biostatistics, School of Public HealthPeking University Health Science CenterBeijingChina
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationBeijingChina
| | | | - Liming Li
- Peking University Center for Public Health and Epidemic Preparedness & ResponseBeijingChina
- Department of Epidemiology and Biostatistics, School of Public HealthPeking University Health Science CenterBeijingChina
- Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationBeijingChina
| | - Zhengming Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
| | - Ling Yang
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
- Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population HealthUniversity of OxfordOxfordUK
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12
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Hu C, Ye X. Dysphagia Caused by Submucosal Tumor-Like Esophageal Cancer: Two Case Reports. Int J Surg Pathol 2025; 33:935-939. [PMID: 39533762 DOI: 10.1177/10668969241291892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Esophageal squamous cell carcinoma is an aggressive and globally prevalent malignancy that rarely presents as submucosal tumor-like lesions, leading to significant diagnostic challenges. We present two examples of primary esophageal squamous cell carcinoma in which complete intramural invasion mimicked submucosal tumor-like lesions. Initial biopsies suggested benign hyperplasia; however, subsequent endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of esophageal squamous cell carcinoma. Both patients received appropriate treatment and showed favorable outcomes. The histopathological feature of intramural esophageal squamous cell carcinoma, characterized by growth confined within the esophageal wall without mucosal epithelial invasion, represents an exceedingly rare and complex pattern. The diagnostic challenges presented by this form of esophageal squamous cell carcinoma highlight the critical role of detailed histopathological examination, with endoscopic ultrasound-guided fine needle aspiration being indispensable for accurate diagnosis and effective management of submucosal tumor-like lesions.
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Affiliation(s)
- Chunxiao Hu
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, P.R. China
| | - Xiaohua Ye
- Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, P.R. China
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13
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Deng X, Luo X, Fang Z, Chen X, Luo Q. Effect of tristetraprolin on esophageal squamous cell carcinoma cell proliferation. Tissue Cell 2025; 94:102785. [PMID: 39954564 DOI: 10.1016/j.tice.2025.102785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/26/2025] [Accepted: 02/03/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Tristetraprolin (TTP) can inhibit the abnormal proliferation of malignant tumors but there are no studies involving TTP and esophageal squamous cell carcinoma (ESCC). We aimed to determine the effect of TTP on ESCC cell proliferation and to elucidate the underlying mechanism. METHODS The human ESCC cell line, KYSE-510, and the human ESCC cell line, KYSE-150, stably infected with tetracycline-inducible expression (Tet-on-TTP and Tet-on-EV, respectively) were screened with puromycin. After Tet-on-TTP KYSE-150 cells were treated with different concentrations of doxycycline [Dox] (0, 0.5, and 1 ug/mL), the levels of TTP mRNA and protein expression were detected by real-time fluorescent quantitative PCR and western blotting, respectively. The effects of TTP on proliferation and migration were estimated by CCK-8 and Transwell assays, respectively. Cell apoptosis and cell cycle were measured by flow cytometry. Cellular apoptosis-related gene protein expression was determined by western blotting. RESULTS TTP overexpression significantly inhibited KYSE-510 and KYSE-150 proliferation. TTP overexpression also significantly inhibited KYSE-150 migration. In addition, TTP expression upregulation promoted the KYSE-150 apoptosis and induced cell cycle arrest in the G2 phase, downregulated Bcl-2 expression, and upregulated Bax expression. CONCLUSION TTP inhibited ESCC cell proliferation, promoted ESCC cell apoptosis, and arrested cell cycle progression in the G2 phase.
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Affiliation(s)
- Xiaoya Deng
- Department of Respiratory Medicine, Shapingba Hospital affiliated to Chongqing University (Shapingba District People's Hospital of Chongqing), Chongqing 400016, China
| | - Xiaoqin Luo
- Out-patient department, Chongqing MingXing Hospital, Chongqing 405200, China
| | - Zhanglan Fang
- General Internal Medicine Department, Chongqing University Cancer Hospital, Chongqing, China
| | - Xinyu Chen
- Department of Pathology, Chongqing University Cancer Hospital, Chongqing, China
| | - Qinli Luo
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.
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14
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Wang H, Yang Y, Li T, Chang S, Zhu Y, Liu C. Drinking Water Temperature Impacts the Pathogenesis of DSS-Induced Ulcerative Colitis by Regulating Intestinal Barrier Function and Remodeling the Gut Microbiota Composition. FASEB J 2025; 39:e70645. [PMID: 40377203 DOI: 10.1096/fj.202500062r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 04/18/2025] [Accepted: 05/07/2025] [Indexed: 05/18/2025]
Abstract
Environmental factors, including poor dietary habits and unhealthy drinking patterns, contribute to ulcerative colitis (UC). While the relationship between diet-related malnutrition and UC has been extensively explored, the impact of drinking water temperature remains largely overlooked, prompting us to investigate its influence on UC pathogenesis and explore the underlying mechanisms. In the present study, we observed that, unlike external thermal and cold therapy, varying drinking water temperatures transiently altered the internal body temperature of the digestive tract. Specifically, chronic drinking of 0°C water had significant anti-inflammatory effects and preserved the integrity of the mucosal barrier in a colitis mouse model. Mechanistically, this temperature spectrum changed the composition of the gut microbiota from inflammation-prone (25°C drinking water) to a resting pattern similar to that of the negative control. Specifically, the abundances of Blautia and Parasutterella, two beneficial genera, were strongly increased in response to 0°C water, accompanied by elevated levels of short-chain fatty acids. In contrast, drinking 40°C water had opposite effects on all the examined parameters and generally aggravated the development of colitis. This study is the first to demonstrate how modifying the temperature of habitual drinking water can modulate colitis progression, providing a novel and noninvasive approach to UC management. Specifically, chronic consumption of 0°C water alleviated the severity of colitis, whereas 40°C water aggravated the disease. Therefore, by focusing on commonly consumed drinking water temperatures, our findings suggest that this simple intervention could be a safe, convenient, and effective therapeutic strategy.
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Affiliation(s)
- Huiting Wang
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Yiheng Yang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Tianyu Li
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Shengyu Chang
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Yao Zhu
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
| | - Chang Liu
- Department of Endocrinology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- Jiangsu Provincial University Key Laboratory of Drug Discovery for Metabolic Inflammatory Diseases, China Pharmaceutical University, Nanjing, China
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15
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Liu B, Wang K, Wang W, Ye S. Analysis of the impact of minimally invasive esophagectomy on quality of life and functional prognosis in patients with esophageal squamous cell carcinoma: A retrospective comparative study. J Cardiothorac Surg 2025; 20:250. [PMID: 40448148 DOI: 10.1186/s13019-025-03485-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 05/18/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND Minimally invasive esophagectomy (MIE) has shown potential benefits in reducing postoperative complications and improving recovery for patients with esophageal squamous cell carcinoma (ESCC). This study aims to assess the effects of MIE on preoperative and postoperative quality of life and functional outcomes in ESCC patients. METHODS Clinical data from 57 ESCC patients who underwent MIE were retrospectively analyzed. Baseline characteristics, including age, gender, BMI, TNM stage, smoking history, alcohol consumption, comorbidities, tumor location, differentiation, and lymph node metastasis, were collected. Postoperative quality of life scores, nutritional status, and functional outcomes were assessed. Paired t-tests and chi-square tests were used to compare preoperative and postoperative variables, while correlation analysis was conducted to evaluate associations between functional outcomes and quality of life. RESULTS A total of 57 patients (41 males, 16 females; mean age: 67.61 ± 7.72 years) who underwent MIE were analyzed. Postoperative evaluation demonstrated significant improvements in quality of life scores across multiple dimensions, including physical symptoms (P = 0.006), emotional management (P = 0.013), role function (P = 0.013), cognitive function (P = 0.042), and social function (P = 0.021). Additionally, nutritional status improved postoperatively, with higher albumin levels (4.12 ± 0.34 g/dL vs. 3.78 ± 0.25 g/dL, P < 0.001) and reduced weight loss (1.98 ± 1.02 kg vs. 2.44 ± 1.12 kg, P = 0.026). Functional outcomes also showed significant improvements, including decreased dysphagia scores (3.45 ± 1.56 vs. 4.04 ± 0.31, P = 0.008), while cardiac physical activity and respiratory function remained stable (P > 0.05). Correlation analysis indicated significant associations between specific functional outcomes and quality of life (P < 0.05). CONCLUSION MIE improves quality of life, nutritional status, and functional outcomes in patients with esophageal squamous cell carcinoma, highlighting its potential benefits in postoperative recovery and patient well-being. TRIAL REGISTRATION Not applicable.
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Affiliation(s)
- Bo Liu
- Thoracic surgery department, The First Affiliated Hospital of Anhui, University of Chinese Medicine, No.117 Meishan Road, Hefei City, 230031, Anhui Province, China.
| | - Kebing Wang
- Thoracic surgery department, The First Affiliated Hospital of Anhui, University of Chinese Medicine, No.117 Meishan Road, Hefei City, 230031, Anhui Province, China.
| | - Wei Wang
- Thoracic surgery department, The First Affiliated Hospital of Anhui, University of Chinese Medicine, No.117 Meishan Road, Hefei City, 230031, Anhui Province, China.
| | - Si Ye
- Thoracic surgery department, The First Affiliated Hospital of Anhui, University of Chinese Medicine, No.117 Meishan Road, Hefei City, 230031, Anhui Province, China.
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16
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Shi L, Wang X, Li C, Bai Y, Zhang Y, Li H. Radiomics applications in the modern management of esophageal squamous cell carcinoma. Med Oncol 2025; 42:221. [PMID: 40425893 DOI: 10.1007/s12032-025-02775-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 05/11/2025] [Indexed: 05/29/2025]
Abstract
Esophageal cancer ranks among the most lethal malignancies globally, with China accounting for more than half of worldwide esophageal squamous cell carcinoma (ESCC) cases. Late-stage diagnosis frequently precludes surgical intervention, contributing to poor outcomes. While precise clinical assessment is essential for treatment planning, therapeutic responses and prognosis exhibit substantial inter-patient heterogeneity, underscoring the urgent need for reliable biomarkers to enhance prognostic accuracy and guide personalized therapeutic strategies. Radiomics, an emerging field that extracts high-dimensional features from medical images, provides non-invasive approaches to improve diagnostic accuracy, predict survival, monitor adverse events, detect recurrence, and optimize treatment strategies. Radiomics has shown promising potential in the modern management of ESCC. Here, we review the critical contributions of radiomics to ESCC research and clinical practice, examining its workflow, applications, strengths, and limitations. Radiomics represents a compelling frontier with substantial potential to advance precision medicine for ESCC patients.
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Affiliation(s)
- Liqiang Shi
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Xipeng Wang
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Chengqiang Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China
| | - Yaya Bai
- Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yajie Zhang
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
| | - Hecheng Li
- Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
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17
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Wang X, Huang J, Xu C, Zhang L, Su J, Liu J, Shen L, Luan L, Hou Y. FGFR3 amplification is predictive of poor prognosis in esophageal squamous cell carcinoma patients. Virchows Arch 2025:10.1007/s00428-024-03884-8. [PMID: 40418326 DOI: 10.1007/s00428-024-03884-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 06/17/2024] [Accepted: 07/27/2024] [Indexed: 05/27/2025]
Abstract
Identification and verification of clinically actionable molecular variations to refine currently adopted risk-stratified treatment strategy for esophageal squamous cell carcinoma (ESCC) is urgently needed. Here, we evaluated FGFR3 amplification status by fluorescence in situ hybridization (FISH) performed on tissue microarrays and its prognostic value in 526 ESCC patients. FGFR3 amplification was found in 3.0% (16/526) of ESCC patients enrolled in this study cohort. Intratumor heterogeneity and metastatic heterogeneity of FGFR3 amplification were found in 10% (2/20) and 40% (2/5) FGFR3 amplified ESCC cases, respectively. No statistically significant associations were found between FGFR3 amplification status and common clinicopathological features. Survival analyses demonstrated that FGFR3 amplification was associated with a worse disease-free survival (DFS) and overall survival (OS) (DFS, P = 0.008; OS, P = 0.027). Univariate and multivariate analyses revealed that invasive depth was significantly associated with DFS (P = 0.001, HR: 1.498, 95% CI: 1.172-1.914) and OS (P = 0.002, HR: 1.482, 95% CI: 1.159-1.894), and FGFR3 amplification was significantly associated with DFS (P = 0.020, HR: 2.065, 95% CI: 1.120-3.808) and tend to associate with OS (P = 0.070, HR: 1.756, 95% CI: 0.954-3.233). Furthermore, when patients were stratified into stage I-II group and stage III-IV group, the adverse effect of FGFR3 amplification on prognosis was presented in stage III-IV patients (DFS, P = 0.0047; OS, P = 0.029) rather than stage I-II patients (DFS, P = 0.46; OS, P = 0.53), indicating that the prognostic value of FGFR3 amplification may relying on clinical stage. Our findings might provide a better understanding of the FGFR3 amplification status in ESCC patients and add further insights into its potential prognostic value.
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Affiliation(s)
- Xiang Wang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Huang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lili Zhang
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jieakesu Su
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Liu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Licheng Shen
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lijuan Luan
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Yingyong Hou
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
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18
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Dai X, Huang H, Liu F. Rapid Identification of Esophageal Squamous Cell Carcinoma Biomarkers by MALDI-TOF MS Fingerprinting of Extracellular Vesicles. Anal Chem 2025; 97:10180-10189. [PMID: 40326690 DOI: 10.1021/acs.analchem.4c06273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Esophageal cancer is a major global health challenge, with high incidence and mortality due to the lack of rapid and sensitive diagnostic tools and specific biomarkers. Cancer-cell-derived extracellular vesicles (EVs) carry unique proteins and nucleic acids, making them valuable sources of cancer biomarkers. We report an integrated method that combines an ultrafast exosome isolation system (EXODUS) with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to detect EVs and identify protein biomarkers for diagnosing and monitoring esophageal squamous cell carcinoma (ESCC). EVs derived from 20 mL culture medium supernatant of ESCC cells with varying degrees of differentiation serve as analysis models. We use EXODUS to isolate EVs rapidly. We then analyze the intact EVs using MALDI-TOF MS, which provides cell line-specific EV fingerprints in minutes. These protein fingerprints allow the discrimination of ESCC from normal control cells and enable the classification of ESCC based on the degree of cell differentiation. We explore critical EV biomarker peaks for ESCC diagnosis (5555 m/z, 8603 m/z, etc.) and monitoring (2268 m/z, etc.). Potential EV biomarker candidates, including YBX1, DIRAS2, HIST1H2AH, and MYBBP1A, are identified through tandem mass tag (TMT) proteomics. We tentatively assign the protein identities of EV marker peaks by correlation with the TMT proteomics. Applying this method to plasma-derived EVs shows promise for rapid, minimally invasive diagnosis and monitoring of ESCC.
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Affiliation(s)
- Xiaodan Dai
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Huiying Huang
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Fei Liu
- National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
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Yuan L, Zhang Y, Wen C, Liu S, Zhang Q, Yin W, Jia Q, Chen M, Luo G, Deng M, Lv M, Xiao W. Esophageal cancer and precancerous lesions: focus on resident bacteria and fungi. Microbiol Spectr 2025:e0313724. [PMID: 40391887 DOI: 10.1128/spectrum.03137-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 03/27/2025] [Indexed: 05/22/2025] Open
Abstract
Accumulating evidence highlights the pivotal role of microbiomes in cancer development. To elucidate the esophageal microbiome's characteristics during esophageal squamous cell carcinoma (ESCC) progression, normal tissues from 13 healthy controls (HC), paired esophageal squamous intraepithelial neoplasia (ESIN) lesional and adjacent (ESINA) tissues from 10 ESIN individuals, and ESCC lesional and adjacent (ESCCA) tissues from 12 ESCC individuals were collected. Following 16S rRNA and ITS sequencing, analyses encompassed α/β-diversity assessments, shared species identification, Type-I Taylor's Power Law Extensions (TPLE), linear discriminant analysis effect size (LEfSe), co-occurrence networks, receiver operating characteristic (ROC) curve analysis, and functional predictions. Distinct microbial signatures characterized HC, precancerous, and cancerous groups. The ESIN group exhibited unique microbial features, including diminished bacterial and fungal species sharing relative to the ESINA group and maximal b values in TPLE for both taxa. Despite the absence of significant bacterial composition differences between HC and ESIN in β-diversity analysis, notable alterations in the oral microbiome were observed. ESIN was marked by Lactobacillus and Aspergillus enrichment, while ESCC was predominantly associated with Fusobacterium, Streptococcus, and Alternaria. Disease progression led to shifts and reductions in species co-occurrence network interactions. Aspergillus demonstrated potential diagnostic value for ESIN, and its ratio to pathogenic functional clusters within network analysis significantly enhanced ESCC detection accuracy. Functional predictions revealed stage-specific pathway enrichments. These findings delineate microbiome alterations across ESCC stages, emphasizing ESIN-specific microbial shifts that may inform microbiome-based strategies for early detection and intervention. IMPORTANCE This study collected esophageal tissues through gastroscopic biopsy and conducted sequencing and analyses to explore the diversity, heterogeneity, key microbial composition, interaction networks, and functional predictions of resident bacteria and fungi in esophageal squamous cell carcinoma (ESCC) progression. The esophageal squamous intraepithelial neoplasia group showed the highest heterogeneity in oral microbiome and fungi, with certain species potentially contributing to ESCC progression. Targeting the oral microbiome in high-risk populations may thus provide a valuable approach for improving early diagnosis and potentially intervening in disease progression.
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Affiliation(s)
- Liping Yuan
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
- Department of Gastroenterology, The First People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, China
| | - Yi Zhang
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Chengli Wen
- Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
- Department of Critical Care Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Sha Liu
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
- Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China
| | - Qin Zhang
- Department of Gastroenterology, The First People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, China
| | - Wen Yin
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Qian Jia
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Maolin Chen
- Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Gang Luo
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Mingming Deng
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
| | - Muhan Lv
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
- Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China
| | - Wanmeng Xiao
- Department of Gastroenterology, The Affiliated Hospital, Southwest Medical University, Luzhou, China
- Human Microecology and Precision Diagnosis and Treatment of Luzhou Key Laboratory, Luzhou, China
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20
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Wang L, Cheng Y, Li W, Wang J, Liu Z, Xiang Y, Liu X, Wang K, Yan D. Knockdown NEK7 stimulates anti-tumor immune responses by NLRP3/PD-L1 signaling in esophageal cancer. Cancer Immunol Immunother 2025; 74:197. [PMID: 40347232 PMCID: PMC12065700 DOI: 10.1007/s00262-025-04057-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2025] [Accepted: 04/14/2025] [Indexed: 05/12/2025]
Abstract
BACKGROUND Esophageal cancer is a prevalent malignancy with limited treatment options. The study aimed to understand the role and mechanism of NEK7 in esophageal cancer development. METHODS RNA sequencing compared esophageal cancer tissues with adjacent tissues, and real-time PCR validated NEK7 expression. Co-IP identified NLRP3 as NEK7's binding partner. We also study the effects of NEK7 knockdown on cell viability, apoptosis, migration, invasion, and the expression of NLRP3/PD-L1 in esophageal carcinoma cell lines. TIMER 2.0 analyzed immune infiltration. An animal model was used to investigate the impact of NEK7 knockdown on tumor size, survival rates, and immune cell infiltration. Licochalcone B blocked NEK7/NLRP3, enhancing CD8 T cell-mediated tumor killing. PD-1's role in T cell viability was also assessed. RESULTS NEK7 was observed to be markedly elevated in both tumor tissues of esophageal cancer and EC109 cells. Moreover, silencing NEK7 reduced cell viability, migration, and invasion, while enhancing cell apoptosis in vitro. Knockdown of NEK7 caused a notable reduction in levels of NLRP3 and PD-L1 in EC109 cells. NEK7 expression showed a positive correlation with immune cell infiltration. Knockdown of NEK7 decreased PD-L1 expression, while upregulation of NEK7 increased PD-L1 expression, then reversed by NLRP3 knockdown. In animal studies, NEK7 knockdown reduced tumor size and volume while improving survival. It also promoted CD4 and CD8 T cell infiltration while inhibiting Treg cells and PD-1 + CD4 and CD8 T cells. Licochalcone B blocked NEK7/NLRP3 binding, decreased cell viability of EC109 cells, and enhanced the activity of co-cultured CD8 T cells. Furthermore, Licochalcone B and anti-PD-1 treatment increased the killing ratio of EC109 cells. CONCLUSION In conclusion, NEK7 is a key regulator in the progression of esophageal cancer and the immune evasion. Targeting the NEK7/NLRP3 pathway may have therapeutic potential for the treatment of esophageal cancer.
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Affiliation(s)
- Li Wang
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Yurong Cheng
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Weiqiang Li
- Department of Thoracic Surgery, Beijing Luhe Hospital of Capital Medical University, Beijing, China
| | - Jing Wang
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Zhe Liu
- Beijing Frontier Research Center for Biological Structure, Department of Thoracic Surgery, School of Basic Medical Sciences, Tsinghua University, Beijing, China
| | - Yaoxian Xiang
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Xin Liu
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Kangjie Wang
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China
| | - Dong Yan
- Department of Oncology, Beijing Luhe Hospital of Capital Medical University, No.82, Xinhua South Road, Tongzhou District, Beijing, 101100, China.
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Wu JD, Wang ZQ, Li QQ, Ren C, Huang S, Fang CY, Wang DS, Chen JY, Tan Q, Li YH, Yang H. Long-term efficacy and progression patterns of paclitaxel plus cisplatin and 5-fluorouracil induction chemotherapy for locally advanced, borderline-resectable esophageal squamous cell carcinoma: results from a phase II NEOCRTEC1601 study. Int J Surg 2025; 111:3299-3305. [PMID: 40146234 PMCID: PMC12165515 DOI: 10.1097/js9.0000000000002360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 03/17/2025] [Indexed: 03/28/2025]
Abstract
INTRODUCTION The NEOCRTEC1601 trial aimed to evaluate the efficacy and safety of paclitaxel in combination with cisplatin and 5-fluorouracil (TPF) as an induction chemotherapy for borderline-resectable esophageal squamous cell carcinoma (BR-ESCC). This study presents an updated 5-year analysis to further elucidate the impact of TPF chemotherapy followed by surgery. METHOD This study was conducted as a single-center, phase II clinical trial. Eligibility was extended to patients diagnosed with BR-ESCC, characterized by a primary tumor or bulky lymph nodes with potential invasion into adjacent organs. The treatment protocol commenced with TPF chemotherapy, followed by surgery, if the tumor was deemed resectable, or by concurrent chemoradiation in cases where resection was not feasible. This updated report delineates the 5-year overall survival (OS) and progression-free survival (PFS) rates. RESULT Surgery was performed on 27 patients (57.4%), and R0 resection was observed in 26 patients (53.2%). Pathologic complete response was confirmed in four patients (8.5%). Following a minimum follow-up period exceeding 60 months for all patients, the total number of deaths was 31 (65.96%). The OS and PFS for the R0 group were significantly longer than those for the non-R0 group (median OS: 53.0 months vs. 13.9 months, HR: 0.36, 95% confidence interval [CI]: 0.17-0.76, P = 0.0032; median PFS: 50.84 months vs. 5.42 months, HR: 0.40, 95% CI 0.19-0.84, P = 0.0076). The 5-year OS rate was 50.0% (34.0%-73.4%) for the R0 group compared to 19.0% (7.9%-46.0%) for the non-R0 group (HR: 0.36, 95% CI: 0.17-0.79, P = 0.0041). CONCLUSION Long-term follow-up confirmed that the OS and PFS were significantly improved in patients who underwent R0 resection compared to those who did not. The 5-year OS rate for patients who achieved R0 resection was 50.0%. R0 resection might be an independent prognostic factor for OS. To further improve the R0 resection rate and prognosis, more effective induction treatment regimens need to be explored.
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Affiliation(s)
- Jia-Di Wu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Zhi-Qiang Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Qiao-Qiao Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Chao Ren
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Sheng Huang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Cai-Yan Fang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - De-Shen Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Ji-Yang Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Qiong Tan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Yu-Hong Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Hong Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
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Pang S, Chen Y, Zheng Z, Wang L, Chen R, He M, Zhao X, Yao J, Jin L. STAT3-orchestrated gene expression signatures and tumor microenvironment in esophageal squamous cell carcinoma uncovered by single-cell sequencing. Biochim Biophys Acta Gen Subj 2025; 1869:130791. [PMID: 40068710 DOI: 10.1016/j.bbagen.2025.130791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 03/04/2025] [Accepted: 03/05/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND The progression of Esophageal Squamous Cell Carcinoma (ESCC) can be dissected with greater precision using multi-omics and single-cell RNA sequencing (scRNA-seq) compared to traditional methodologies. These advanced approaches enable a comprehensive understanding of cellular heterogeneity and molecular dynamics, offering higher resolution insights into cancer development. Moreover, analyzing transcription factor regulatory networks provides innovative avenues for identifying cancer biomarkers and therapeutic targets, driving new perspectives in cancer research. OBJECTIVE To explore the molecular mechanisms and cellular dynamics of ESCC. METHODS Utilizing bulk-RNA-seq and single-cell transcriptomics, our study identify major cell types, transcriptomic gene and function changes during ESCC progression. Validation experiments in clinical sample tissues and ESCC cell lines to confirm core regulation factor in ESCC. RESULTS We identified six major cell types in the ESCC scRNA-seq dataset and revealed profound shifts in cellular composition and transcriptional profiles. Notably, STAT3 was found to be a core regulator in ESCC and negatively regulated LHPP expression at promoter sites. Elevated STAT3 and reduced LHPP expression were consistently observed in patient samples, highlighting their inverse relationship in ESCC pathogenesis. CONCLUSION This study integrates bulk-seq and scRNA-seq data to reveal the pivotal role of STAT3 in ESCC. STAT3 negatively regulates LHPP expression, driving tumor progression. These findings underscore the therapeutic potential of targeting STAT3 in ESCC. KEY WORDS ESCC, single-cell transcriptomics, ESCC microenvironment, STAT3.
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Affiliation(s)
- Shilian Pang
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China
| | - Yurao Chen
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China
| | - Zemao Zheng
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China
| | - Luoshai Wang
- Department of Thoracic Surgery, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China
| | - Ronghuai Chen
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China
| | - Ming He
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China
| | - Xiang Zhao
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China
| | - Juan Yao
- Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223299, Jiangsu, China; Department of Radiation Oncology, Huaian Cancer Hospital, Huaian 223299, Jiangsu, China.
| | - Liyan Jin
- Department of Oncology, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213000, Jiangsu, China; Department of Oncology, The Wujin Clinical college of Xuzhou Medical University, Changzhou 213000, Jiangsu, China.
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23
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Xiao H, Zhou T, Yang Y, Yang X, Bi Y, Cheng X. LncRNA-DANCR Promotes ESCC Progression and Function as ceRNA to Regulate DDIT3 Expression by Sponging microRNA-3193. Cancer Sci 2025; 116:1324-1338. [PMID: 40071783 PMCID: PMC12044675 DOI: 10.1111/cas.70035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 02/13/2025] [Accepted: 02/22/2025] [Indexed: 05/02/2025] Open
Abstract
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of cancer development and progression. Among them, Differentiation Antagonizing Non-Protein Coding RNA (DANCR) has been implicated in various malignancies, including esophageal squamous cell carcinoma (ESCC). This study explores the clinical characteristics, prognostic implications, functional roles, and molecular mechanisms of DANCR in ESCC. Our results demonstrate that DANCR is highly expressed in ESCC, and acts as an oncogene in ESCC both in vitro and in vivo. Through bioinformatics analysis and experimental validation, we revealed that DANCR promotes ESCC progression by sponging miR-3193 and regulating its target gene DDIT3 expression. These findings highlight the critical role of DANCR in the development of ESCC and suggest its potential as a prognostic predictor and drug therapeutic target.
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Affiliation(s)
- Heng Xiao
- Translational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal CancerShanxi Medical UniversityTaiyuanShanxiChina
- Key Laboratory of Cellular Physiology of the Ministry of Education, Department of PathologyShanxi Medical UniversityTaiyuanShanxiChina
| | - Tong Zhou
- Shanxi Academy of Medical ScienceShanxi Medical UniversityTaiyuanChina
| | - Yanfang Yang
- Translational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal CancerShanxi Medical UniversityTaiyuanShanxiChina
- The School of Public HealthBaotou Medical CollegeBaotouInner MongoliaChina
| | - Xin Yang
- Translational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal CancerShanxi Medical UniversityTaiyuanShanxiChina
- Key Laboratory of Cellular Physiology of the Ministry of Education, Department of PathologyShanxi Medical UniversityTaiyuanShanxiChina
| | - Yanghui Bi
- Center of Gene Sequencing, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanChina
| | - Xiaolong Cheng
- Translational Medicine Research Center, Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal CancerShanxi Medical UniversityTaiyuanShanxiChina
- Key Laboratory of Cellular Physiology of the Ministry of Education, Department of PathologyShanxi Medical UniversityTaiyuanShanxiChina
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24
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Cao Y, Huang S, He Y, Zhang Y, Chen S, Huang M, He F, Chen S, Wang D, Yang Z, Zhao X, Wang X, Wu Z, Ao M, Qiu Y, Fang M. Discovery of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine derivatives as novel cyclin-dependent kinase 12 (CDK12) inhibitors for the treatment of esophageal squamous cell carcinoma. Bioorg Chem 2025; 158:108302. [PMID: 40056603 DOI: 10.1016/j.bioorg.2025.108302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 02/11/2025] [Accepted: 02/19/2025] [Indexed: 03/10/2025]
Abstract
The transcriptional cyclin-dependent protein kinase 12 (CDK12), a potential target in various cancers, was recently discovered with a dramatic amplification in esophageal cancer (EC). In this study, we conducted an online database analysis that revealed CDK12 to be overexpressed in esophageal squamous cell carcinoma (ESCC) tissue samples from patients. Furthermore, survival analysis indicated that CDK12 can serve as a prognostic indicator for ESCC patients. In addition, CDK12 knockdown had been shown to reduce the proliferation of ESCC cells. The present study also details the design, synthesis, and biological evaluation of new CDK12 inhibitors which bear the scaffold of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine. Among the synthesized compounds, H63 has been identified as a potent inhibitor of CDK12 with excellent anti-ESCC activity. Mechanistically, H63 blocked transcription elongation, downregulated the G1-phase core genes to induce cell cycle arrest, and altered the CDK12-ATM/ATR-CHEK1/CHEK2 signaling axis to cause DNA damage. In addition, H63 exhibited favorable pharmacokinetic properties, good safety, and prominent anti-ESCC activity in vivo. The present study suggests that CDK12 is a promising target for ESCC treatment, and H63 is a promising candidate for further clinical development as an anti-ESCC drug.
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Affiliation(s)
- Yin Cao
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Sen Huang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Yaohui He
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; MOE Key Lab of Rare Pediatric Diseases, Hengyang Medical School, University of South China, Hengyang 421001, China
| | - Yuxiang Zhang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Simian Chen
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Mengxian Huang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; Technical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China
| | - Fengming He
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Shutong Chen
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Di Wang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Benxi 117004, China
| | - Ziying Yang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Xinwei Zhao
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China
| | - Xiumin Wang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Zhen Wu
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
| | - Mingtao Ao
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China; School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China.
| | - Yingkun Qiu
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
| | - Meijuan Fang
- State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
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25
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Wang X, Guan P, You L, Qin W, Li Q, Wang X, Chen Q, Yu D, Ye Y, Wang T, Liu X, Fan J, Xu G. Risk of serum circulating environmental chemical residues to esophageal squamous cell carcinoma: a nested case-control metabolome-wide association study. Anal Bioanal Chem 2025; 417:2783-2795. [PMID: 39939416 DOI: 10.1007/s00216-025-05784-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/26/2025] [Accepted: 02/03/2025] [Indexed: 02/14/2025]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the primary histological subtype of esophageal carcinoma, yet research on environmental exposure risks and associated metabolic alterations preceding ESCC is limited. In a nested case-control cohort of 396 adults (199 diagnosed with ESCC and 197 healthy controls (HC)), we combined exposomics and metabolomics to assess circulating chemical residues and early serum metabolic changes linked to ESCC risk. A cell experiment further evaluated the proliferative impact of 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTS), identifying it as a risk factor for ESCC, primarily through lipid metabolism-related chronic inflammation. Significant metabolic disruptions were observed in ESCC cases, characterized by increased carnitines, phosphatidylcholines (PCs), and triglycerides (TGs) alongside reduced lysophosphatidylcholines (LPCs) and ether lysophosphatidylcholines (LPC-Os). An early-warning biomarker panel, including glutamic acid, methionine, choline, LPC-O 18:0, TG (14:0_18:2_20:5), and PC (18:0_20:4)/LPC 18:0, showed improved predictive capacity when combined with 6:2 FTS. Metabolome-exposome-wide association studies largely confirmed 6:2 FTS as a potential ESCC risk factor through lipid mediation. This study offers novel insights for ESCC prevention and early diagnosis through a combined biomarker panel integrating metabolic and environmental risk indicators.
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Affiliation(s)
- Xiaokun Wang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pengwei Guan
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Lei You
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Wangshu Qin
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qi Li
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiaolin Wang
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qianqian Chen
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Di Yu
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yaorui Ye
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Ting Wang
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xinyu Liu
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Jinhu Fan
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Guowang Xu
- State Key Laboratory of Medical Proteomics, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China
- Liaoning Province Key Laboratory of Metabolomics, Dalian, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
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Nakao A, Kawakubo H, Takeuchi M, Matsuda S, Fukuda K, Kitagawa Y. Risk factors for pneumonia after endoscopic laryngopharyngeal surgery in cases with prior esophageal cancer treatment. Ann Gastroenterol Surg 2025; 9:456-463. [PMID: 40385341 PMCID: PMC12080194 DOI: 10.1002/ags3.12907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 12/06/2024] [Accepted: 12/22/2024] [Indexed: 05/20/2025] Open
Abstract
Background and Study Aims Endoscopic laryngopharyngeal surgery is an effective treatment for superficial laryngopharyngeal cancer, particularly in cases with prior esophageal cancer treatment. Despite its frequent application, reports on the risk factors for postoperative complications are limited. This study aimed to identify the risk factors for pneumonia after endoscopic laryngopharyngeal surgery and to examine the variations in pneumonia incidence among the types of prior esophageal cancer treatment. Methods Patients who had a history of esophageal cancer treatment and subsequently underwent endoscopic laryngopharyngeal surgery for superficial pharyngolaryngeal cancer were retrospectively analyzed. We examined the association between postoperative pneumonia and several factors, including number of lesions; diameter of the resected lesion; and type of previous esophageal cancer treatment, such as endoscopic submucosal dissection, chemoradiotherapy, and esophagectomy. Results The study included 79 patients who had a mean age of 67.4 years. Postoperative pneumonia occurred in 16.4%. Multivariate analysis showed that the pneumonia incidence significantly increased in cases with multiple lesions (OR 4.794, 95% CI 1.133-20.288, p = 0.033) and larger diameter of the resected lesion (OR 7.047, 95% CI 1.791-27.730, p = 0.005). Importantly, compared with other treatments, prior esophagectomy for esophageal cancer did not increase the pneumonia incidence. Conclusions Multiple lesions and larger lesion diameter were the significant predictors of postoperative pneumonia. Moreover, endoscopic laryngopharyngeal surgery can be safely performed even in patients who have previously undergone esophageal cancer surgery, although careful monitoring remains necessary.
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Affiliation(s)
- Atsushi Nakao
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | | | - Masashi Takeuchi
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Satoru Matsuda
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Kazumasa Fukuda
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Yuko Kitagawa
- Department of SurgeryKeio University School of MedicineTokyoJapan
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Zhang G, Zhang Y, Chen S, Guo H, Qi X, Li B, Wang J, Wang C. Establishment of a prognostic nomogram for evaluating non-adjuvant therapy in patients with stage I to III esophageal cancer: a population-based study. J Thorac Dis 2025; 17:2206-2216. [PMID: 40400928 PMCID: PMC12090151 DOI: 10.21037/jtd-24-1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 01/24/2025] [Indexed: 05/23/2025]
Abstract
Background According to reports from China, esophageal cancer ranked sixth in terms of morbidity and accounted for 6.26% of all cancer cases in China. This study aimed to establish an effective prognostic nomogram for non-adjuvant therapy in patients with stage I to III esophageal cancer. Methods We took up cases from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database and used R language software to perform Kaplan-Meier survival curve and multivariate Cox regression analysis. Furthermore, we established the nomogram for non-adjuvant therapy patients with stage I to III esophageal cancer to predict 3- and 5-year esophageal cancer-specific survival rate. The prognostic ability of the nomogram was assessed using the C-index, area under the receiver operating characteristic (ROC) curve, and calibration chart. Results The esophageal cancer-specific survival rate of cancer in the lower third of the esophagus was significantly higher than that of cancers in the upper-third of the esophagus as per the Kaplan-Meier curve. Based on the multivariate Cox regression analysis, sub variables such as advanced age, stage II and III, squamous cell carcinoma, moderately differentiated (grade II), poorly differentiated (grade III), and undifferentiated (grade IV) cancer significantly increased risk of prognosis in all patients. With a total of 150 points in the nomogram, the 3- and 5-year esophageal cancer-specific survival rates were 50% and 40% respectively. The value of C-index of this model was 0.851 and the value of the area under receiver operating curve projected 1-, 3-, and 5-year esophageal cancer-specific survival rates of 0.884, 0.874, and 0.856, respectively. Conclusions The established nomogram had good prediction ability for non-adjuvant therapy patients with stage I to III esophageal cancer.
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Affiliation(s)
- Guanglei Zhang
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Yan Zhang
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Shu Chen
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Hang Guo
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Xiao Qi
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Baofeng Li
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Jincheng Wang
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
| | - Chunguang Wang
- Department of Thoracic Surgery, Second Hospital Affiliated of Jilin University, Changchun, China
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Yang Q, Lv S, Li Q, Lan L, Liu N, Wang M, Sun X, Feng X, Han K. Neoadjuvant arterial infusion chemotherapy combined with immunotherapy in treating locally advanced lower esophageal and esophagogastric junction cancer. J Thorac Dis 2025; 17:2273-2285. [PMID: 40400978 PMCID: PMC12090167 DOI: 10.21037/jtd-24-1908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 02/19/2025] [Indexed: 05/23/2025]
Abstract
Background The treatment of locally advanced lower esophageal cancer/esophagogastric junction cancers still has certain limitations. This study shares a new therapeutic strategy, namely neoadjuvant arterial infusion chemotherapy combined with immunotherapy (neo-AICIT). Methods The data of patients who received neoadjuvant arterial infusion chemotherapy (docetaxel + cisplatin) combined with immunotherapy (tislelizumab) for locally advanced lower esophageal cancer or esophagogastric junction cancers from October 2021 to May 2023 were collected. The indicators of these patients, such as the clinical staging of tumors, treatment-related adverse events (TRAEs), the effect of neoadjuvant therapy, operative complications, tumor regression grade (TRG), progression-free survival (PFS), and follow-up time, were recorded. Results A total of 12 patients received a complete neoadjuvant regimen, sequential surgery, and postoperative maintenance immunotherapy. The median age was 61.5 years. All patients suffered from squamous cell carcinoma; eight of them had lower esophageal cancer and four had esophagogastric junction cancer. The clinical staging in all patients was cT3N0-2M0G1-3. The median tumor proportion score (TPS) was 32.5%. Only grade 1 TRAEs occurred during adjuvant therapy, and the incidence was 58.3% (7/12). Postoperative complications included pulmonary infection 16.7% (2/12) and recurrent laryngeal nerve injury 16.7% (2/12). The postoperative pathology showed that 11 (91.7%, 11/12) patients had major pathological remission (MPR) with a TRG of 1-2, while 7 (58.3%, 7/12) patients had pathological complete response (pCR) with a TRG of 1. The objective response rate (ORR) was 100%. The median follow-up time was 19.5 months. Two patients had mediastinal lymph node metastasis at 18 and 20 months after operation, respectively. Tumor recurrence or metastasis was not found in other patients. Conclusions Observations of small case series suggest that neo-AICIT has good safety and efficacy in the treatment of locally advanced lower esophageal/esophagogastric cancer, and may be a promising neoadjuvant treatment option.
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Affiliation(s)
- Qingjie Yang
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Shenghua Lv
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Qingtian Li
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Linhui Lan
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Ningquan Liu
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Mingyang Wang
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Xiaoyan Sun
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Xinhai Feng
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
| | - Kaibao Han
- Department of Thoracic Surgery, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, China
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Morais R, Afonso J, Sousa N, Sousa-Pinto B, Libânio D, Marinho B, Sacramento ML, Simplício M, Faria-Ramos I, Azevedo L, Marques M, Silveira H, Gullo I, Carneiro F, Santos-Antunes J, Macedo G. Cost-utility and clinical impact of endoscopic screening for esophageal and gastric neoplasia in patients with head and neck neoplasms. Eur J Gastroenterol Hepatol 2025; 37:00042737-990000000-00524. [PMID: 40359284 PMCID: PMC12122095 DOI: 10.1097/meg.0000000000002988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/30/2025] [Indexed: 05/15/2025]
Abstract
OBJECTIVE Patients with head and neck neoplasms (HNN) are at an increased risk of esophageal neoplasia (EN) and gastric neoplasia (GN). We aimed to assess the clinical impact and cost-utility of endoscopic screening in this population in the Western setting. METHODS In this single-center study HNN patients eligible for curative treatment underwent screening esophagogastroduodenoscopy. We assessed the frequency, clinical, and pathological outcomes of EN and GN. The cost-effectiveness of an annual endoscopic screening for EN was evaluated from a societal perspective, using a Markov model and probabilistic sensitivity analysis. In addition, we performed a sensitivity analysis using data on the prevalence of detected EN lesions in the four largest previous Western studies on this topic. RESULTS Forty-six HNN patients met the inclusion criteria and underwent endoscopic screening. Six EN were detected in five patients (10.9%, 95% confidence interval: 1.9-19.9%). Additionally, five GN were detected in five patients. Most patients had early-stage EN or GN (90%) and were treated with endoscopic resection (80%). Endoscopic screening strategy had an incremental cost-effectiveness ratio of 39 357.8 €/quality-adjusted life years gained, being cost-effective at a willingness-to-pay threshold of two times the Portuguese gross domestic product per capita. In the sensitivity analysis, it remained cost-effective when considering the prevalence of EN reported in Germany, France, and Brazil. CONCLUSION An endoscopic screening program identified EN or GN in a fifth of HNN patients, most presenting at an early stage. The program implementation appears to be cost-effective in Portugal. These results may be applicable to other medium-to-high-income Western countries.
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Affiliation(s)
- Rui Morais
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
| | - João Afonso
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
| | - Nuno Sousa
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
| | - Bernardo Sousa-Pinto
- MEDCIDS, Department of Community Medicine, Information and Health Decision Sciences
- CINTESIS@RISE-Health Research Network, Faculty of Medicine, University of Porto
| | - Diogo Libânio
- MEDCIDS, Department of Community Medicine, Information and Health Decision Sciences
- Gastroenterology Department, RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) and Porto Comprehensive Cancer Center (Porto CCC)
| | | | | | | | | | | | - Margarida Marques
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
| | - Helena Silveira
- Faculty of Medicine
- Department of Otorhinolaryngology and Head and Neck Surgery, Unidade Local de Saúde São João
| | - Irene Gullo
- Faculty of Medicine
- Department of Pathology
- IPATIMUP/i3S, University of Porto, Porto, Portugal
| | - Fátima Carneiro
- Faculty of Medicine
- Department of Pathology
- IPATIMUP/i3S, University of Porto, Porto, Portugal
| | - João Santos-Antunes
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
- IPATIMUP/i3S, University of Porto, Porto, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology, Unidade Local de Saúde São João
- Faculty of Medicine
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Wang XM, Liu CT, Huang JT, Zhang ZH, Xu YW, Wu FC, Peng YH. Development and validation of a prognostic model for patients with cT1-4N1-3M1 esophageal squamous cell carcinoma: based on the SEER database and the Chinese cohort study. Front Oncol 2025; 15:1547462. [PMID: 40356748 PMCID: PMC12066260 DOI: 10.3389/fonc.2025.1547462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
Objective The purpose of this study was to investigate the impact of clinicopathological factors on the overall survival (OS) of advanced esophageal squamous cell carcinoma (ESCC) patients with both lymph node and distant metastasis and build a nomogram for OS prediction. Method We selected 621 ESCC patients with cT1-4N1-3M1 stage without surgical treatment from the Surveillance, Epidemiology, and End Results (SEER) database and randomized (in a 7:3 ratio) to the training cohort and internal validation cohort. Another 159 patients were enrolled from the Cancer Hospital of Shantou University Medical College as the external validation cohort. A nomogram was developed based on independent risk factors that resulted from a multivariate Cox regression analysis. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the discriminative ability and calibration curves were constructed to evaluate the calibration ability. Kaplan-Meier survival analysis and log-rank tests were then used to predict the further OS status of these patients. Results The multivariate Cox regression analysis revealed that sex, T stage, radiotherapy, and chemotherapy were independent prognostic factors for ESCC patients with cT1-4N1-3M1 stage. All these factors were incorporated to construct a nomogram. The prognostic nomogram in training cohort exhibited the AUCs of 0.784, 0.746, and 0.735 for predicting 6-, 9-, and 12-month OS, respectively. Calibration curves exhibited that the nomogram-predicted OS were insistent with the actual OS. In validation cohorts, the nomogram still showed acceptable discrimination ability and calibration. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort. The OS of the high-risk group was shorter than that of the low-risk group in three cohorts. Conclusion We developed and validated an individualized survival prediction nomogram for predicting OS in ESCC patients with cT1-4N1-3M1 stage, which may help clinicians to assess the situation of advanced ESCC patients and implement further treatment.
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Affiliation(s)
- Xiao-Mei Wang
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
| | - Jia-Tao Huang
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Zhi-Han Zhang
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yi-Wei Xu
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
| | - Fang-Cai Wu
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
- Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Yu-Hui Peng
- Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Esophageal Cancer Prevention and Control Research Center, The Cancer Hospital of Shantou University Medical College, Shantou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
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Ding X, Li Y, Wang X, Li F, Xu Z, Zhu Y, Chen Z. Down-regulation of YAP prevents smoking- and alcohol-induced carcinogenesis of esophageal paracancerous tissue by promoting cellular pyroptosis. Sci Rep 2025; 15:14766. [PMID: 40295580 PMCID: PMC12037795 DOI: 10.1038/s41598-025-98952-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Accepted: 04/16/2025] [Indexed: 04/30/2025] Open
Abstract
Paracancerous tissues (PCTs) were previously considered benign regions, but recent findings reveal genomic instability in these areas. Smoking and alcohol consumption are closely associated with esophageal cancer (EC) development. This study explored the interplay between the Hippo pathway and pyroptosis in EC, PCTs, and distal normal tissues (DNTs). We used molecular epidemiological methods to analyze the effects of smoking and alcohol on these pathways. We found that key genes in both pathways were more altered in smokers and/or drinkers compared to non-smokers and non-drinkers. Additionally, we observed changes in some genes and proteins in PCTs, while the Hippo pathway and pyroptosis had not yet been influenced. We applied 4.0% alcohol combined with various concentrations of cigarette smoke extract (CSE) to PCTs cultured in vitro to observe carcinogenesis and changes in these pathways. Verteporfin, as an inhibitor of YAP, was also used in vitro culture experiments to observe its effects on cellular carcinogenesis. Among 56 EC patients, 41 had a history of smoking and/or alcohol consumption in this study. Compared to DNTs, Hippo pathway genes (Lats1, Yap, and Taz) and pyroptosis genes (Nlrp3, Asc, Gsdmd, and Caspase-1) were altered in 49 EC tissues, while changes of Lats1, Nlrp3, and Asc were observed in 47 PCTs. Additionally, 4.0% alcohol combined with 3.2%, 4.0%, and 5.8% CSE, respectively, not only induced cellular heterogeneity and even cancerous transformation, but also suppressed the Hippo pathway and pyroptosis in the PCTs cultured in vitro. Furthermore, in vitro, 9 μM verteporfin inhibited cellular heterogeneity/carcinogenesis in PCTs induced by 4.0% alcohol combined with 5.8% CSE through inhibiting YAP and promoting pyroptosis. It is speculated that the downregulation of YAP could prevent smoking- and alcohol-induced carcinogenesis in esophageal PCTs by promoting pyroptosis, which may offer new insights for the treatment of esophageal squamous carcinoma.
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Affiliation(s)
- Xinyu Ding
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
| | - Ying Li
- Department of Pathology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Xuning Wang
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha, 410013, China
| | - Fan Li
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha, 410013, China
| | - Zhifei Xu
- Department of Thoracic Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China
| | - Yongfei Zhu
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Medical School, Hunan Normal University, Changsha, 410013, China.
| | - Zihao Chen
- Department of Thoracic Surgery, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
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Xu Z, Sun B, Wang W, Fan Y, Su J, Sun J, Gu X. Research progress on m6A and drug resistance in gastrointestinal tumors. Front Pharmacol 2025; 16:1565738. [PMID: 40356985 PMCID: PMC12066682 DOI: 10.3389/fphar.2025.1565738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 04/21/2025] [Indexed: 05/15/2025] Open
Abstract
Gastrointestinal (GI) tumors represent a significant global health burden and are among the leading causes of cancer-related mortality worldwide. their drug resistance is one of the major challenges in cancer therapy. In recent years, epigenetic modifications, especially N6-methyladenosine (m6A) RNA modifications, have become a hot research topic. m6A modification plays an important role in gene expression and cancer progression by regulating RNA splicing, translation, stability, and degradation, which are regulated by "writers," "erasers" and "readers." In GI tumors, resistance to chemotherapy, targeted therapy, and immunotherapy is closely associated with m6A RNA modification. Therefore, the molecular mechanism of m6A modification and its targeted drug development provide new therapeutic strategies for overcoming drug resistance and therapeutic efficacy in GI tumors. In this review, the biological functions of m6A were explored, the specific resistance mechanisms of m6A in different types of GI tumors were explored, new ideas and targets for future treatment resistance were identified, and the limitations of this field were highlighted.
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Affiliation(s)
| | | | | | | | | | - Jiachun Sun
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Xinyu Gu
- Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
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Li Y, Wang Y, Ren G, Yu H, Yin Y, Ma L, Yu X, Chen W, Zhang K, Zhao Y, Liu Z. Characterization of novel mouse esophageal squamous cell carcinoma cell lines and their utility as preclinical models. Cancer Lett 2025; 616:217600. [PMID: 40024567 DOI: 10.1016/j.canlet.2025.217600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 03/04/2025]
Abstract
Esophageal squamous cell carcinoma (ESCC) has a high incidence, poor treatment response, and high mortality. Subcutaneous transplant tumor models are commonly used to study the immunosuppressive tumor microenvironment and its impact on immunotherapy. In this study, we established two new ESCC mouse cell lines, mEC525M and mEC586F, from 4NQO-induced ESCC mouse models of different sexes. We compared their proliferation, motility, and molecular characteristics with existing lines (HNM007, AKR, mEC25) using in vitro experiments and whole-exome sequencing. Treatment sensitivity analysis of all murine ESCC tumor cell lines revealed that AKR and HNM007 cells were more responsive to chemotherapy, mEC25 cells were more sensitive to radiotherapy, whereas mEC525M and mEC586F cells exhibited greater sensitivity to immunotherapy. Multiplex immunohistochemistry (mIHC) staining analysis revealed differences in immune infiltration among the tumors derived from the five mouse ESCC cell lines, with the highest proportion of T cells in mEC525M tumors, the highest proportion of CD11b+ myeloid cells in mEC586F tumors and the highest proportion of CD19+ B cells in mEC25 tumors. In addition, RNA sequencing results also revealed differences in immune responses exhibited by tumor tissues derived from the five mouse ESCC cell lines after anti-PD1 treatment. Therefore, this study offers a valuable tool for investigating the immune microenvironment in ESCC and supports the selection of mouse models for preclinical ESCC research.
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Affiliation(s)
- Yang Li
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yuhao Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Guanzhu Ren
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hui Yu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yin Yin
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lei Ma
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiao Yu
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Wangtianjiao Chen
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Kai Zhang
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yahui Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Zhihua Liu
- State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Ding Y, Zhou L, He X, Li L, Wang X. Rhomboid Domain Containing 2 (RHBDD2) is Upregulated and Responds to Cisplatin-Induced DNA Damage in Esophageal Cancer. Biochem Genet 2025:10.1007/s10528-025-11118-y. [PMID: 40295376 DOI: 10.1007/s10528-025-11118-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 04/22/2025] [Indexed: 04/30/2025]
Abstract
As a pseudoprotease, RHBDD2 regulates tumor survival and progression in several cancers, but its expression and function in most cancers remain unclear. This study aimed to investigate the role of RHBDD2 in esophageal carcinoma (ESCA) via the use of public datasets and performing cytology experiments and RNA-seq analysis in ESCA cells. RHBDD2 was obviously upregulated and contributed to worse relapse-free survival (RFS) in patients with ESCA. Furthermore, chemotherapy increased RHBDD2 expression, and several GEO datasets also demonstrated that RHBDD2 expression was upregulated in both cisplatin-treated and resistant ESCA cells. Additionally, cytology experiments revealed that cisplatin treatment markedly upregulated the expression of RHBDD2 and γH2AX, which is a DNA damage marker, whereas RHBDD2 knockdown or overexpression affected cisplatin-induced γH2AX expression and the cytotoxic effects of cisplatin. The functional enrichment of RNA-seq data from RHBDD2-knockdown EC9706 cells suggested that RHBDD2-induced DEGs were involved in the DNA damage response and repair. Pearson's correlation analysis revealed that RHBDD2 expression was positively correlated with the expression of several genes, such as DMC1, CBX5, RAD1, DDB2, and ERCC1, which are responsible for DNA damage repair. Taken together, our results first revealed that RHBDD2 is upregulated and responds to DNA damage in ESCA, which provides new evidence for the potential role of RHBDD2 in the chemotherapy sensitivity and survival of patients with ESCA.
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Affiliation(s)
- Youxiang Ding
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
| | - Lin Zhou
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Xintao He
- Department of Pathology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China
| | - Lin Li
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China
| | - Xiaoping Wang
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211100, China.
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Yuan XC, Jia P, Tian T, Zhu J, Zhang XY. Endoscopic submucosal dissection for esophageal precancerous lesions and early esophageal carcinoma: Analysis of efficacy and serum tumor markers. World J Gastrointest Surg 2025; 17:103700. [PMID: 40291880 PMCID: PMC12019039 DOI: 10.4240/wjgs.v17.i4.103700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/25/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Tumor progression in patients with esophageal precancerous lesions (EPLs) or early esophageal carcinoma (EEC) is typically confined in both extent and location. Prompt and effective intervention significantly improves treatment outcomes and prognosis for these individuals. AIM To determine the effect of endoscopic submucosal dissection (ESD) on efficacy, serum tumor markers (STMs), and 6-month postoperative recurrence rate in patients with either EPL or EEC. METHODS This study initially enrolled 120 patients with EPL or EEC, who were admitted from April 2021 to April 2024. Participants were divided into the control group (60 cases), which underwent thoracotomy, and the research group (60 cases) which received ESD treatment. The comparative analysis involved information regarding the efficacy (dissection area and resection rate per unit time), complications (delayed bleeding, wound infection, esophageal reflux, and postoperative esophageal stenosis), surgery-related parameters (bleeding volume, operation duration, and hospital length of stay), STMs [carcinoembryonic antigen (CEA), carbohydrate antigen 724 (CA724), and tumor-specific growth factor (TSGF)], and the 6-month postoperative recurrence rate of the two groups. RESULTS Data indicated statistically higher dissection area and resection rate per unit of time in the research group than in the control group. Meanwhile, the research group demonstrated a notably lower overall incidence rate of complications, bleeding volume, operation duration, and hospital length of stay. Further, the CEA, CA724, and TSGF were markedly reduced in the research group after treatment, which were statistically lower compared to the baseline and those of the control group. Finally, during the follow-up, a comparable 6-month postoperative recurrence rate was determined in the two groups. CONCLUSION ESD is clinically effective and safe for EPL and EEC and can significantly restore abnormally increased levels of STMs.
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Affiliation(s)
- Xiao-Chen Yuan
- Department of Gastroenterology, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Taizhou 225300, Jiangsu Province, China
| | - Ping Jia
- Department of Gastroenterology, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Taizhou 225300, Jiangsu Province, China
| | - Tian Tian
- Department of Laboratory Medicine, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Taizhou 225300, Jiangsu Province, China
| | - Jun Zhu
- Department of Gastroenterology, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Taizhou 225300, Jiangsu Province, China
| | - Xiao-Yan Zhang
- Department of Gastroenterology, The Affiliated Taizhou Second People’s Hospital of Yangzhou University, Taizhou 225300, Jiangsu Province, China
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Zheng H, Tan J, Qin F, Zheng Y, Yang X, Liu Z, Cai W, Qin X, Liao H. PKM2 modulates chemotherapy sensitivity by regulating autophagy and predicts the prognosis and immunity in pancancer. Sci Rep 2025; 15:14626. [PMID: 40287473 PMCID: PMC12033356 DOI: 10.1038/s41598-025-96562-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
One of the main characteristics of tumor metabolite reprogramming is enhanced glycolysis, and Pyruvate Kinase M2(PKM2) is a crucial enzyme that limits the pace of glycometabolism. Although PKM2 has been proven to affect the development of some cancers, a pan-cancer analysis of PKM2 has not yet been performed. We analyzed the expression and prognosis of PKM2 in pan-cancer using multiple databases. We performed epigenetic, functional enrichment, immune cell infiltration, immune checkpoint, and drug sensitivity analyses of PKM2. PKM2 was found to be significantly upregulated in most malignancies and associated with a bad prognosis. In some cancers, the PKM2 DNA promoter was hypomethylated. The expression of PKM2 was positively linked with most m6A-methylation-related genes in pan-cancer. The functions of PKM2 were primarily associated with the regulation of the immune system, glycolysis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. PKM2 was favorably associated with neutrophils and cancer-associated fibroblasts in the tumor microenvironment of most cancers. Importantly, PKM2 showed a strikingly high correlation with CD274 (PD-L1), CD276, TGF-β1, VEGFA, and HAVCR2 in most cancers. Finally, using experiments, it was confirmed that silencing PKM2 could increase the sensitivity of esophageal squamous cell carcinoma to cisplatin by regulating autophagy. PKM2 affects autophagy - regulated tumor cell tolerance to chemotherapy, providing future research directions for solving tumor chemotherapy resistance.
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Affiliation(s)
- Haosheng Zheng
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Jian Tan
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Fei Qin
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Yuzhen Zheng
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xingping Yang
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Zui Liu
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Weijie Cai
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xianyu Qin
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
| | - Hongying Liao
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
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Zhang X, Wang Z, Zhao Y, Ye H, Li T, Wang H, Sun G, Liang F, Dai L, Wang P, Liu X. Multi-omics analysis unveils a four-gene prognostic signature in esophageal squamous carcinoma and the therapeutic potential of PKP1. BMC Cancer 2025; 25:777. [PMID: 40281492 PMCID: PMC12032815 DOI: 10.1186/s12885-025-14150-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies, characterized by high heterogeneity and poor outcomes. Effective classification for patient stratification and identifying reliable markers for prognosis prediction and treatment choice are crucial. METHODS Integration of single-cell RNA-sequencing (RNA-seq) and bulk RNA-seq analyses were used to characterize ESCC. Non-negative matrix factorization (NMF) clustering was performed to stratify the ESCC patients into different subtypes and the clinical and pathological features of the ESCC subtypes were compared. Cox regression analysis and LASSO regression analysis were used to select key genes and construct a risk model for ESCC. The associations of the key genes with anti-cancer drug sensitivities in ESCC cell lines were investigated. RT-qRCR experiments, proteomics analysis, and multiplex immunohistochemistry (mIHC) experiments were used to validate the results. Furthermore, one identified gene was selected to investigate its correlation with EGFR expression and the gene effect scores of various potential gene targets across pan-cancer. RESULTS The study identified the dysregulated distributions of epithelial cells and fibroblasts as characteristic of ESCC. ESCC patients could be classified into four distinct subtypes with unique cell type features and prognoses. With the gene makers of the cell type features, a four-gene prognostic signature for ESCC was constructed. The CCND1-PKP1-JUP-ANKRD12 model could effectively discriminate the survival status of ESCC patients, independent of various pathological and clinical features. The risk score for the samples was correlated with the expression levels of immunoregulatory genes. The prognostic effects of CCND1, PKP1, and JUP were confirmed at the protein level. The phosphorylation levels of PKP1, JUP, and ANKRD12 were found to be dysregulated in ESCC tumors. Their expression dysregulation and heterogeneity were demonstrated in ESCC cell lines. All four genes were significantly correlated with at least one of the anti-cancer drug sensitivities in ESCC cell lines. PKP1 expression was significantly correlated with EGFR expression and gene effect scores in multiple cancers. CONCLUSIONS We conclude that the CCND1-PKP1-JUP-ANKRD12 signature may serve as a novel indicator for ESCC prognosis and diagnosis. PKP1 expression might provide new clues for gene therapy efficacy in multiple cancers.
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Affiliation(s)
- Xiuzhi Zhang
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China
| | - Zhi Wang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Yutong Zhao
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Tiandong Li
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China
| | - Han Wang
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China
| | - Guiying Sun
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China
| | - Feifei Liang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, 4500001, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
| | - Xiaoli Liu
- Laboratory Department, Henan Provincial People's Hospital, Zhengzhou, 450003, China.
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Li R, Yang Y, Gao Y, Lv J, Dai C, Zhai Y, Mao C, Jiang J, Fan J, Yu Y, Wu L, Lin Z. Knowledge map of programmed cell death in esophageal cancer: a bibliometric analysis. Discov Oncol 2025; 16:609. [PMID: 40274628 PMCID: PMC12022209 DOI: 10.1007/s12672-025-02376-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025] Open
Abstract
OBJECTIVES This study aimed to delineate the evolving knowledge structure of programmed cell death in esophageal cancer and identify key thematic trends, influential collaborations, and emerging areas for future research. METHODS A bibliometric approach was applied to 2677 publications retrieved from the Web of Science Core Collection (2000-2024). Three complementary tools-CiteSpace, VOSviewer, and bibliometrix-were employed to visualize co-citation networks, detect citation bursts, and map collaborative patterns among authors, institutions, and countries. Inclusion criteria focused on articles and reviews that addressed esophageal cancer in conjunction with apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, or related pathways. RESULTS Publication outputs grew markedly, reflecting a shift from early investigations of basic apoptotic mechanisms to broader explorations of necroptosis, pyroptosis, and ferroptosis. China led in publication volume and citations, driven by substantial governmental funding and large clinical cohorts. The United States and Japan also contributed significantly, forming international research networks that spanned Asia and Europe. Leading institutions, particularly Zhengzhou University, demonstrated extensive collaborations. Journals such as Oncology Letters and Oncology Reports were prominent outlets for new findings, while highly cited references highlighted hypoxia, immune checkpoint blockade, and emerging gene-editing strategies. Keyword analyses revealed the ascendance of immuno-oncology, network pharmacology, and translational applications targeting multiple regulated cell death pathways. CONCLUSION Bibliometric evidence underscores a rapid expansion of multidisciplinary research that integrates diverse cell death pathways in esophageal cancer. Continued international collaborations, leveraging advanced genomics and immunologic strategies, are poised to accelerate translational breakthroughs and enable more personalized, effective therapies.
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Affiliation(s)
- Rulin Li
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yanchun Yang
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yang Gao
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jing Lv
- Department of Orthopedics, Ziyang Central Hospital, Ziyang, 641300, China
| | - Chuanqiang Dai
- Department of Orthopedics, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yuanwei Zhai
- Department of Medical Imaging, Ziyang Central Hospital, Ziyang, 641300, China
| | - Chirong Mao
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jiudong Jiang
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jiangang Fan
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yang Yu
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Liang Wu
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Zhiwu Lin
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China.
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Huang X, You R, Liu F, Jian Z, Zhou G, Yin H, Wu M, Sun T, Duan Z, Xu W, Zhang S, Yang X, Jiao H, Yang S, Wang Q, Yin J, Tang H, Lin M, Tan L. Identification and validation of poor prognosis immunoevasive subtype of esophageal cancer with tumor-infiltrating SAMD3 + NK cell abundance. Cancer Immunol Immunother 2025; 74:177. [PMID: 40252130 PMCID: PMC12009252 DOI: 10.1007/s00262-025-04028-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 03/19/2025] [Indexed: 04/21/2025]
Abstract
INTRODUCTION Esophageal cancer (EC) remains highly lethal due to tumor microenvironment (TME)-mediated immune evasion. While natural killer (NK) cells are central to antitumor immunity, their functional states in EC are poorly characterized. METHODS We integrated bulk RNA-seq (TCGA/GEO) and single-cell data to construct an NK cell-derived prognostic signature (NK score) via LASSO-Cox regression. Immunofluorescence was applied to assess the clinical relevance of SAMD3 + NK cells in EC. Using both xenograft mouse models and in vitro co-culture procedures, the impact of SAMD3 on NK cell function was confirmed. RESULTS In EC patients, the prognostic NK score-which is generated from important NK cell markers including SAMD3-was substantially correlated with a worse chance of survival. NK cells within the TME had significant levels of SAMD3 expression, as seen by immunofluorescence labeling. Moreover, NK cells with SAMD3 knockdown exhibited enhanced antitumor activity, leading to decreased tumor development in the xenograft model. DISCUSSION Our results demonstrate the predictive significance of NK cell markers in EC and pinpoint SAMD3 as a critical modulator of NK cell activity. We pioneer SAMD3 + NK cells as architects of TME immunosuppression in EC. Our findings nominate SAMD3 inhibition as a combinatorial strategy to overcome immune checkpoint blockade resistance.
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Affiliation(s)
- Xu Huang
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Runze You
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Fangyi Liu
- The School of Basic Medical Sciences, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Zitao Jian
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Guanyou Zhou
- The School of Basic Medical Sciences, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Hao Yin
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Mengyuan Wu
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Tiantao Sun
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Zhiyun Duan
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Wenyi Xu
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Shaoyuan Zhang
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Xinyu Yang
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Heng Jiao
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Shuyi Yang
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Qingle Wang
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Jun Yin
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Han Tang
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Miao Lin
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
- The School of Basic Medical Sciences, Fudan University, Shanghai, China.
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
| | - Lijie Tan
- Departments of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
- The School of Basic Medical Sciences, Fudan University, Shanghai, China.
- Departments of Thoracic, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
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Zhang X, Du J, Lin X, Zhang S, Zeng T, Chen M, Huang G, Chen C, Zheng B. Identification of disulfidptosis in esophageal squamous cell carcinoma based on single-cell and bulk RNA-seq data to predict prognosis and treatment response. Front Immunol 2025; 16:1567793. [PMID: 40303412 PMCID: PMC12037556 DOI: 10.3389/fimmu.2025.1567793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/18/2025] [Indexed: 05/02/2025] Open
Abstract
Purpose Our study aims to identify the molecular subtypes of genes associated with disulfidptosis in esophageal squamous cell carcinoma(ESCC), develop a prognostic model, and identify potential therapeutic targets. Methods Based on the GSE53625 expression profile data, we identified molecular subtypes with significant survival differences through consensus cluster analysis. Subsequently, univariate Cox, multivariate Cox, and LASSO-Cox regression analysis were used to establish risk stratification models. The transcriptome data of the TCGA-ESCC cohort and the GSE160269 single-cell sequencing dataset were integrated to verify the biological significance of the model, and further analyze the heterogeneity of the tumor immune microenvironment, explore the differences in the intercellular communication network, and screen potential targeted drugs, providing a theoretical basis for subsequent translational research. Results We identified two distinct patterns of disulfidptosis expression with significant differences in overall survival. Then, we constructed the prognostic signature of disulfidptosis, and results showed patients with high score had worse prognosis. Univariate and multivariate Cox analysis demonstrated that the constructed prognostic signature was an independent prognostic factor and was validated in an independent validation set. The two subgroups differed in the proportion of immune cell infiltration and related signaling pathways in ESCC. The exploration of immunotherapy data confirmed our prognostic signature also had certain predictive power for immunotherapy. Drug screening suggested AZD8186 and JQ1 as potential therapies for high-score patients. Conclusion This study provides a new prognostic signature for ESCC, explores new therapeutic targets, and provides new theoretical support for personalized treatment.
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Affiliation(s)
- Xiaodan Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Jianting Du
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Xiao Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Shuliang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Taidui Zeng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Maohui Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Guanglei Huang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
| | - Bin Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China
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41
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Liu S, Lin Z, Huang Z, Yu M, Lin Z, Hu Z. Unique Microbial Characterisation of Oesophageal Squamous Cell Carcinoma Patients with Different Dietary Habits Based on Light Gradient Boosting Machine Learning Classifier. Nutrients 2025; 17:1340. [PMID: 40284204 PMCID: PMC12030675 DOI: 10.3390/nu17081340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/29/2025] Open
Abstract
Objectives: The microbiome plays an important role in cancer, but the relationship between dietary habits and the microbiota in oesophageal squamous cell carcinoma (ESCC) is not clear. The aim of this study is to explore the complex relationship between the microbiota in oesophagal tissue and dietary habits in ESCC patients. Methods: 173 ESCC patients were included. The method of 16S rRNA sequencing was used to analyze microbial composition and diversity. The LEfSe and Boruta methods were used to screen important microbes, and the LightGBM algorithm distinguished microbes associated with different dietary habits. PICRUST2 and DESeq2 predicted microbial function and screened differential functions. The Pearson test was used to analyze correlations between microbes and functions, and SPARCC microbial symbiotic networks and Cytoscape were used to determine microbial interactions. Results: Significant differences in microbial composition were observed among ESCC patients with different dietary habits. LEfSe and Boruta identified three, six, and two significantly different bacteria in the FF/FP, FF/PF, and FF/PP groups, respectively, with AUC values of 0.683, 0.830, and 0.715. PICRUST2 and DESeq2 analysis revealed 3, 11, and 5 significantly different metabolic pathways in each group. Eubacterium_B sulci was positively correlated with PWY-6285, PWY-3801, and PWY-5823. PWY-6397 was positively correlated with undefinded (Fusobacterium_C). Microbial network analysis confirmed unique microbial characteristics in different diet groups. Conclusions: Different dietary habits lead to alterations in Eubacterium_B sulci and undefinded (Fusobacterium_C) and related functional pathways.
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Affiliation(s)
- Shun Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhifeng Lin
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhimin Huang
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Menglin Yu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zheng Lin
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China; (S.L.); (Z.L.); (Z.H.); (M.Y.); (Z.L.)
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350122, China
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Lemay F, Sandhu AS, Stein BD, Goodwin R. A Canadian algorithm for upper gastrointestinal cancer management. Front Oncol 2025; 15:1548637. [PMID: 40297809 PMCID: PMC12034531 DOI: 10.3389/fonc.2025.1548637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open
Abstract
Recent advances in immunotherapy have changed the treatment landscape for cancers of the upper gastrointestinal (GI) system. Immune checkpoint inhibitors can lead to better survival and improved quality of life for affected individuals. Adopting new treatment strategies in real-world practice can be challenging, and algorithms that are easy to implement in Canadian oncology practices would benefit clinicians and patients. In this study, we present expert opinion on best practices for upper GI cancer management, including a new algorithm that integrates the latest evidence for screening, workup, diagnosis, treatment, and survivorship. The algorithm is based on a novel approach comprising a case-based, accredited educational program with asynchronous discussion among clinicians practicing across Canada, with the input of expert medical oncologists and gastroenterologists. A needs assessment was employed to determine current areas of educational need in the field of upper GI cancers, and a patient representative provided insights into patient concerns and priorities. The best practices described here include seeking patient input throughout treatment, integrating immune checkpoint inhibitors into systemic therapy for both localized and advanced disease, and providing comprehensive supportive care throughout the treatment and survivorship journey.
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Affiliation(s)
- Frédéric Lemay
- Division of Gastroenterology, Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Amindeep S. Sandhu
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | | | - Rachel Goodwin
- Division of Medical Oncology, Department of Medicine, University of Ottawa, The Ottawa Hospital Regional Cancer Centre, Ottawa, ON, Canada
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43
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Wang J, Zhang Z, Song L, Liu X, He X. Inhibition of esophageal squamous cell carcinoma progression by MIR210HG and activation of the P53 signaling pathway to promote apoptosis and autophagy. Eur J Med Res 2025; 30:269. [PMID: 40211342 PMCID: PMC11987309 DOI: 10.1186/s40001-025-02512-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 03/26/2025] [Indexed: 04/13/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) stands among the frequently occurring malignancies. The lack of efficient early detection methods and therapeutic approaches leads to a high mortality rate for ESCC. The long noncoding RNA MIR210HG is strongly related to various malignant tumors. However, its involvement in ESCC remains unexplored. Thus, this investigation aimed to assess the involvement of MIR210HG in ESCC development. METHODS The MIR210HG expression was analyzed in numerous tumor types through pan-cancer analysis of The Cancer Genome Atlas(TCGA) database. This research investigated the MIR210HG role in the survival and prognosis of individuals with ESCC. The biological functions of MIR210HG were examined by enrichment analyses, including GO, GSEA, and KEGG. Moreover, immune cell infiltration, tumor microenvironment (TME) characteristics, and immune checkpoint expression levels associated with MIR210HG were explored. To get more insight into the connection between MIR210HG and ESCC, we assessed related gene and protein expression using Western blotting and qRT-PCR. To evaluate the proliferation, invasion, migration, apoptosis, and autophagy of ESCC cells, various techniques were employed, including EdU proliferation tests, monodansylcadaverine (MDC) staining, wound healing assays, cell colony formation, transwell assays, flow cytometry, and an established xenograft mouse model. RESULTS MIR210HG exhibited low expression levels in ESCC. High expression of MIR210HG correlated with a higher survival rate among patients. The elevated expression of MIR210HG hindered the ESCC cell's ability to proliferate, invade, and migrate, both in vivo and in vitro settings. Furthermore, a positive correlation between MIR210HG and the P53 signaling pathway was observed, which could affect autophagy and apoptosis in ESCC cells. CONCLUSIONS MIR210HG emerges as a pivotal gene in ESCC, influencing both the immunity and prognosis of patients. Moreover, it may affect autophagy and apoptosis via the P53 signaling pathway. Overall, these outcomes present novel ideas for ESCC treatment.
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Affiliation(s)
- Jianyu Wang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
- Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China
| | - Zhenhu Zhang
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Liang Song
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Xiangyan Liu
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China
| | - Xiaopeng He
- Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, 250021, Shandong Province, China.
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Chen S, Zhou S, Wu L, Chen S, Liu S, Li H, Ruan G, Liu L, Chen H. Incorporating frequency domain features into radiomics for improved prognosis of esophageal cancer. Med Biol Eng Comput 2025:10.1007/s11517-025-03356-4. [PMID: 40208480 DOI: 10.1007/s11517-025-03356-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/23/2025] [Indexed: 04/11/2025]
Abstract
Esophageal cancer is a highly aggressive gastrointestinal malignancy with a poor prognosis, making accurate prognostic assessment essential for patient care. The performance of the esophageal cancer prognosis model based on conventional radiomics is limited, as it mainly characterizes the spatial features such as texture of the tumor area, and cannot fully describe the complexity of esophageal cancer tumors. Therefore, we incorporate the frequency domain features into radiomics to improve the prognostic ability of esophageal cancer. Three hundred fifteen esophageal cancer patients participated in the death risk prediction experiment, with 80% being the training set and 20% being the testing set. We use fivefold cross validation for training, and fuse the 5 trained models through voting to obtain the final prognostic model for testing. The CatBoost achieved the best performance compared to machine learning methods such as random forests and decision tree. The experimental results showed that the combination of frequency domain and radiomics features achieved the highest performance in death predicting esophageal cancer (accuracy: 0.7423, precision: 0.7470, recall: 0.7375, specification: 0.8030, AUC: 0.8487), which was significantly better than the performance of frequency domain or radiomics features alone. The results of Kaplan-Meier survival analysis validated the performance of our method in death predicting esophageal cancer. The proposed method provides technical support for accurate prognosis of esophageal cancer.
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Affiliation(s)
- Shu Chen
- School of Life & Environmental Science, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Shumin Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
| | - Liyang Wu
- School of Life & Environmental Science, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Shuchao Chen
- School of Life & Environmental Science, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Shanshan Liu
- School of Life & Environmental Science, Guilin University of Electronic Technology, Guilin, 541004, China
| | - Haojiang Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
| | - Guangying Ruan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China
| | - Lizhi Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong Esophageal Cancer Institute, Guangzhou, 510060, China.
| | - Hongbo Chen
- School of Life & Environmental Science, Guilin University of Electronic Technology, Guilin, 541004, China.
- Guangxi Human Physiological Information Noninvasive Detection Engineering Technology Research Center, Guilin, 541004, China.
- Guangxi Colleges and Universities Key Laboratory of Biomedical Sensors and Intelligent Instruments, Guilin, 541004, China.
- Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Guilin, 541004, China.
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Ma T, Liu GQ, Guo J, Ji R, Shao XJ, Li YQ, Li Z, Zuo XL. Artificial intelligence-aided optical biopsy improves the diagnosis of esophageal squamous neoplasm. World J Gastroenterol 2025; 31:104370. [PMID: 40248066 PMCID: PMC12001168 DOI: 10.3748/wjg.v31.i13.104370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/24/2025] [Accepted: 03/10/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Early detection of esophageal squamous neoplasms (ESN) is essential for improving patient prognosis. Optical diagnosis of ESN remains challenging. Probe-based confocal laser endomicroscopy (pCLE) enables accurate in vivo histological observation and optical biopsy of ESN. However, interpretation of pCLE images requires histopathological expertise and extensive training. Artificial intelligence (AI) has been widely applied in digestive endoscopy; however, AI for pCLE diagnosis of ESN has not been reported. AIM To develop a pCLE computer-aided diagnostic system for ESN and assess its diagnostic performance and assistant efficiency for nonexpert endoscopists. METHODS The intelligent confocal laser endomicroscopy (iCLE) system consists of image recognition (based on inception-ResNet V2), video diagnosis, and quality judgment modules. This system was developed using pCLE images and videos and evaluated through image and prospective video recognition tests. Patients between June 2020 and January 2023 were prospectively enrolled. Expert and non-expert endoscopists and the iCLE independently performed diagnoses for pCLE videos, with histopathology as the gold standard. Thereafter, the non-expert endoscopists performed a second assessment with iCLE assistance. RESULTS A total of 25056 images from 2803 patients were selected for iCLE training and validation. Another 2442 images from 226 patients were used for testing. iCLE achieved a high accuracy of 98.3%, sensitivity of 95.3% and specificity of 98.8% for diagnosing ESN images. A total of 2581 patients underwent upper gastrointestinal pCLE examination and were prospectively screened; 54 patients with suspected ESN were enrolled. Overall, 187 videos from 67 lesions were assessed by iCLE, three nonexpert and three expert endoscopists. iCLE achieved a high accuracy, sensitivity and specificity of 90.9%, 92.0%, and 90.2%, respectively. Compared to experts, iCLE showed significantly higher sensitivity (92.0% vs 80.4%; P < 0.001) and negative predictive value (94.4% vs 87.7%; P = 0.003). With iCLE assistance, nonexpert endoscopists showed significant improvements in accuracy (from 83.6% to 88.6%) and sensitivity (from 76.0% to 89.8%). CONCLUSION iCLE system demonstrated high diagnostic performance for ESN. It can assist nonexpert endoscopists in improving the diagnostic efficiency of pCLE for ESN and has the potential for reducing unnecessary biopsies.
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Affiliation(s)
- Tian Ma
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Guan-Qun Liu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Jing Guo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Rui Ji
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xue-Jun Shao
- Qingdao Medicon Digital Engineering Company Limited, Qingdao 266000, Shandong Province, China
| | - Yan-Qing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Zhen Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Yuan Q, Shi Y, Wang J, Xie Y, Li X, Zhao J, Jiang Y, Qiao Y, Guo Y, Zhang C, Lu J, Zhao T, Dong Z, Li P, Dong Z, Liu K. p38 mediated ACSL4 phosphorylation drives stress-induced esophageal squamous cell carcinoma growth through Src myristoylation. Nat Commun 2025; 16:3319. [PMID: 40195298 PMCID: PMC11976994 DOI: 10.1038/s41467-025-58342-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 03/18/2025] [Indexed: 04/09/2025] Open
Abstract
The comprehension of intricate molecular mechanisms underlying how external stimuli promote malignancy is conducive to cancer early prevention. Esophageal squamous cell carcinoma (ESCC) is considered as an external stimuli (hot foods, tobacco, chemo-compounds) induced cancer, characterized by stepwise progression from hyperplasia, dysplasia, carcinoma in situ and invasive carcinoma. However, the underlying molecular mechanism governing the transition from normal epithelium to neoplastic processes in ESCC under persistent external stimuli has remained elusive. Herein, we show that a positive correlation between p38 and ERK1/2 activation during the progression of ESCC. We identify that phosphorylation of ACSL4 at T679 by p38 enhances its enzymatic activity, resulting in increased production of myristoyl-CoA (C14:0 CoA). This subsequently promotes Src myristoylation and activates downstream ERK signaling. Our results partially elucidate the role of ACSL4 in mediating stress-induced signaling pathways that activate growth cascades and contribute to tumorigenesis.
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Affiliation(s)
- Qiang Yuan
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
| | - Yunshu Shi
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
| | - Junyong Wang
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China
| | - Yifei Xie
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Xiaoyu Li
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China
| | - Jimin Zhao
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Yanan Jiang
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Yan Qiao
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Yaping Guo
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Chengjuan Zhang
- Center of Bio-Repository, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Lu
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Tongjin Zhao
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China
- State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Zhongshan Hospital, Fudan University, Shanghai Qi Zhi Institute, Shanghai, China
| | - Ziming Dong
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China
| | - Peng Li
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China.
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China.
| | - Zigang Dong
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China.
| | - Kangdong Liu
- The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
- State Key Laboratory of Metabolic dysregulation & the Prevention and Treatment of Esophageal Cancer, Zhengzhou, Henan, China.
- Tianjian Laboratory for Advanced Biomedical Sciences, Zhengzhou, Henan, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China.
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Huang C, Li Y, He C. Oral microbes and gastrointestinal cancers: new strategies and insights. Clin Transl Oncol 2025:10.1007/s12094-025-03891-4. [PMID: 40186840 DOI: 10.1007/s12094-025-03891-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 02/25/2025] [Indexed: 04/07/2025]
Abstract
Gastrointestinal (GI) cancers are among the most prevalent cancers globally and represent a leading cause of cancer-related mortality. A distinctive characteristic of these cancers is their association with the microbes. Gut microbiota dysbiosis is widely recognized as a contributing factor in cancer development. Recent advancements in molecular techniques have increasingly underscored the role of oral microbes in GI cancers, especially colorectal cancer. Oral microbes, transported to the gut via swallowed saliva, have been shown to influence GI health. Both in vivo and in vitro investigations demonstrated the impacts of oral microbes in GI cancers. This review explores the changes in oral microbial diversity and relative abundance in esophageal, gastric and colorectal cancers as well as the underlying mechanisms. These mechanisms include immunomodulation, epigenetics, apoptosis, and others. Among these, immunomodulation stands out due to its close connection with cancer treatment. Finally, we discuss the limitations of the current research and propose new perspectives and directions for future studies.
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Affiliation(s)
- Chenlu Huang
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
- HuanKui Academy, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yu Li
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China
- HuanKui Academy, Nanchang University, Nanchang, Jiangxi Province, China
| | - Cong He
- Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yong Waizheng Street, Donghu District, Nanchang, 330006, Jiangxi Province, China.
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Liu M, Huang Y, Tian H, Guo C, Liu Z, Liu A, Yang H, Li F, Duan L, Shen L, Wu Q, Shi C, Pan Y, Liu F, Liu Y, Chen H, Hu Z, Cai H, He Z, Ke Y. Absolute Risk Prediction for Esophageal Squamous Cell Carcinoma Adaptable to Regional Disease Burden across Diverse Regions. Cancer Epidemiol Biomarkers Prev 2025; 34:510-517. [PMID: 39869045 DOI: 10.1158/1055-9965.epi-24-1465] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/03/2024] [Accepted: 01/21/2025] [Indexed: 01/28/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) exhibits a long latency period and has a significant geographic disparity in incidence, which underscores the need for models predicting the long-term absolute risk adaptable to the regional disease burden. METHODS A total of 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above cases identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: (i) constructing a relative risk model using logistic regression, (ii) calculating the age-specific baseline hazard, and (iii) adjusting for the competing risk of all-cause death excluding ESCC. Flexible incidence rate parameters were integrated into the model to ensure its relevance across diverse regions worldwide. RESULTS A total of 295 severe dysplasia and above cases were detected. The relative risk model consisted of old age, male gender, an irregular meal pattern, a preference for hot or hard food, a BMI of less than 22 kg/m2, and ESCC family history. The AUC was 0.753 (95% confidence interval, 0.749-0.757). The averaged 5-and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator and incorporated flexible incidence rate parameters, demonstrating ideal risk stratification tailored to regions with varying disease burdens (https://pkugenetics.shinyapps.io/escc_risk_prediction/). CONCLUSIONS We developed an absolute risk model to predict individualized long-term risk of ESCC, accounting for the local disease burden. IMPACT This model has the potential to mitigate the global burden of ESCC by enabling targeted screening and personalized prevention strategies.
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Affiliation(s)
- Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yi Huang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongrui Tian
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chuanhai Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Anxiang Liu
- Endoscopy Center, Anyang Cancer Hospital, Anyang, China
| | - Haijun Yang
- Department of Pathology, Anyang Cancer Hospital, Anyang, China
| | - Fenglei Li
- Hua County People's Hospital, Hua County, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Qi Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Endoscopy Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chao Shi
- People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Huanyu Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhe Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhonghu He
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Ke
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
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49
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Song P, Tian W, Zheng Y, Xu S, Hu Z, Jin X, Zhu X, Tan L, Chen D, Chen Y. Genomic and Immune Profiling of Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Therapy Versus Upfront Surgery Identifies Novel Immunogenic Cell Death-Based Signatures for Predicting Clinical Outcomes. MedComm (Beijing) 2025; 6:e70171. [PMID: 40182138 PMCID: PMC11965704 DOI: 10.1002/mco2.70171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 02/02/2025] [Accepted: 02/26/2025] [Indexed: 04/05/2025] Open
Abstract
It remains undetermined regarding the impact of neoadjuvant therapy on immunogenic cell death (ICD) and subsequent tumor microenvironment (TME) remodeling in esophageal squamous cell carcinoma (ESCC). And it is of paramount significance to identify beneficiaries from neoadjuvant therapy in treatment-naïve ESCC. In this study, 88 ESCC samples undergoing neoadjuvant therapy plus surgery (NA+S) or surgery alone (SA) were subjected to bulk-RNA sequencing. A five-gene RINscore incorporating ICD-related signature genes with TME-based hub genes was established to predict clinical outcomes and pharmacological responses, in which SLAMF7 and IL1R1 were selected out as co-expressed genes. The regulatory mechanism of the repressive co-transcription factor BATF of SLAMF7 and IL1R1 was further demonstrated. Our data demonstrated that NA+S led to high abundance in kinds of T helper cells, nature killer T cells and M1-like macrophages with increased CD8+T cells infiltration compared with SA. ICD phenotypes were further characterized in treatment-naïve ESCC to determine their differences in TME and potential benefits from NA. Our findings not only offered novel insights into the distinct TME and ICD profiles of ESCC undergoing different therapeutic modes, but also provided the RINscore, which may aid oncologists in determining individualized (neo)adjuvant immunotherapy regimen.
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Affiliation(s)
- Peidong Song
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Wenze Tian
- Department of Thoracic Surgerythe Affiliated Huai'an First People's Hospital of Nanjing Medical UniversityHuai'anChina
| | - Yujia Zheng
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Sukai Xu
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Zihao Hu
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Xing Jin
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Xuejuan Zhu
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Lijie Tan
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Donglai Chen
- Department of Thoracic SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Yongbing Chen
- Department of Thoracic Surgerythe Second Affiliated Hospital of Soochow UniversitySuzhouChina
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50
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Inoue-Choi M, Ramirez Y, O'Connell C, Berrington de Gonzalez A, Dawsey SM, Abnet CC, Freedman ND, Loftfield E. Hot beverage intake and oesophageal cancer in the UK Biobank: prospective cohort study. Br J Cancer 2025; 132:652-659. [PMID: 39972189 PMCID: PMC11961563 DOI: 10.1038/s41416-025-02953-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 12/18/2024] [Accepted: 02/03/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Drinking maté, a type of tea consumed at a very hot temperature in South America has been considered as a risk factor for oesophageal squamous cell carcinoma (ESCC). METHODS We assessed daily intake and preferred temperature of hot beverages (tea and coffee) in relation to incident ESCC (n = 242) and adenocarcinoma (EAC; n = 710) among 454,796 adults in the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression. RESULTS Relative to non-drinkers and warm temperature drinkers (referent group), drinking 4-6 cups/d (HR, 1.97; 95% CI, 1.14-3.38) or more of hot temperature beverages was associated with higher risk of ESCC; HRs increased with increasing daily intake of hot temperature beverages (P-trend < 0.01). ESCC risk was still higher for those who drank very hot beverages; drinking ≤ 4 cups/d was associated with a 2.5-fold higher risk (HR, 2.52; 95% CI, 1.27-5.03), and risk increased with increasing daily intake of very hot temperature beverages (P-trend < 0.01). There was no clear association for EAC. CONCLUSIONS Our findings provide new evidence that drinking hot or very hot beverages is a risk factor for ESCC in the UK where drinking hot tea and coffee is common.
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Affiliation(s)
- Maki Inoue-Choi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA.
| | - Yesenia Ramirez
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
| | - Caitlin O'Connell
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
| | | | - Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
| | - Christian C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
| | - Erikka Loftfield
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD, USA
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