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Chen C, Wang J, Zhu X, Zhang S, Yuan X, Hu J, Liu C, Liu L, Zhang Z, Li J. Lactylation as a metabolic epigenetic modification: Mechanistic insights and regulatory pathways from cells to organs and diseases. Metabolism 2025; 169:156289. [PMID: 40324589 DOI: 10.1016/j.metabol.2025.156289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/20/2025] [Accepted: 04/30/2025] [Indexed: 05/07/2025]
Abstract
In recent years, lactylation, a novel post-translational modification, has demonstrated a unique role in bridging cellular metabolism and epigenetic regulation. This modification exerts a dual-edged effect in both cancer and non-cancer diseases by dynamically integrating the supply of metabolic substrates and the activity of modifying enzymes: on one hand, it promotes tissue homeostasis and repair through the activation of repair genes; on the other, it exacerbates pathological progression by driving malignant phenotypes. In the field of oncology, lactylation regulates key processes such as metabolic reprogramming, immune evasion, and therapeutic resistance, thereby shaping the heterogeneity of the tumor microenvironment. In non-cancerous diseases, including neurodegeneration and cardiovascular disorders, its aberrant activation can lead to mitochondrial dysfunction, fibrosis, and chronic inflammation. Existing studies have revealed a dynamic regulatory network formed by the cooperation of modifying and demodifying enzymes, and have identified mechanisms such as subcellular localization and RNA metabolism intervention that influence disease progression. Nevertheless, several challenges remain in the field. This article comprehensively summarizes the disease-specific regulatory mechanisms of lactylation, with the aim of providing a theoretical foundation for its targeted therapeutic application.
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Affiliation(s)
- Cong Chen
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Jie Wang
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China.
| | - Xueying Zhu
- Department of Anatomy, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Shan Zhang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Xiandun Yuan
- Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100096, China
| | - Jun Hu
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Chao Liu
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Lanchun Liu
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China
| | - Zhenpeng Zhang
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China.
| | - Jun Li
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing 100053, China.
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Shatila M, Sperling G, Machado AP, Vohra M, Baerman E, Toni END, Török HP, Zhao D, Zhou Y, Shafi MA, Thomas AS, Alasadi M, Wang Y. Helicobacter pylori infection negatively affects response of gastric cancer to immunotherapy. Ann Gastroenterol 2025; 38:262-269. [PMID: 40371204 PMCID: PMC12070332 DOI: 10.20524/aog.2025.0966] [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: 11/04/2024] [Accepted: 04/07/2025] [Indexed: 05/16/2025] Open
Abstract
Background Helicobacter pylori (H. pylori) is a known risk factor for gastric cancer, possibly via the PD-1/L1 pathway, and this infection may reduce the efficacy of immune checkpoint inhibitors (ICIs). This study explored the effects of H. pylori infection status on survival outcomes in patients with gastric cancer. Methods This single-center, retrospective study included patients with gastric adenocarcinoma between June 1985 and August 2022. Patients with different histological subtypes were excluded. Primary variables of interest included H. pylori infection status and treatment with ICIs. Other clinical information included demographics, cancer histology, the presence of other cancers, and vital status. Results A total of 2930 patients were included, of whom 206 (7.0%) received ICIs, 196 (6.7%) had prior H. pylori infection, and 1037 (35.4%) had a diffuse subtype. Diffuse cancer subtypes were associated with better survival (P<0.05) at 3 and 5 years compared to intestinal-type adenocarcinomas. Diffuse cancers demonstrated better survival outcomes than intestinal cancers at 10 years, but only among H. pylori-positive patients (P=0.013). H. pylori positivity was associated with worse survival at 3 years (P=0.041) among patients taking ICIs, but not in those not receiving ICIs (P=0.325). Conclusions These findings suggest H. pylori infection may be an obstacle to successful immunotherapy, and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of H. pylori positivity in gastric cancer.
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Affiliation(s)
- Malek Shatila
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Malek Shatila, Mehnaz A. Shafi, Anusha Shirwaikar Thomas, Mazen Alasadi, Yinghong Wang)
| | - Gabriel Sperling
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX, USA (Gabriel Sperling)
| | - Antonio Pizuorno Machado
- Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USA (Antonio Pizuorno Machado, Muhammad Vohra)
| | - Muhammad Vohra
- Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USA (Antonio Pizuorno Machado, Muhammad Vohra)
| | - Elliot Baerman
- Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA (Elliot Baerman)
| | - Enrico N. De Toni
- Department of Medicine II, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany (Enrico N. De Toni, Helga-Paula Török)
| | - Helga-Paula Török
- Department of Medicine II, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany (Enrico N. De Toni, Helga-Paula Török)
| | - Dan Zhao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Dan Zhao)
| | - Yan Zhou
- Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Yan Zhou)
| | - Mehnaz A. Shafi
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Malek Shatila, Mehnaz A. Shafi, Anusha Shirwaikar Thomas, Mazen Alasadi, Yinghong Wang)
| | - Anusha Shirwaikar Thomas
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Malek Shatila, Mehnaz A. Shafi, Anusha Shirwaikar Thomas, Mazen Alasadi, Yinghong Wang)
| | - Mazen Alasadi
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Malek Shatila, Mehnaz A. Shafi, Anusha Shirwaikar Thomas, Mazen Alasadi, Yinghong Wang)
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (Malek Shatila, Mehnaz A. Shafi, Anusha Shirwaikar Thomas, Mazen Alasadi, Yinghong Wang)
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Yang HC, Fu CF, Qiao LJ, Long GH, Yang LF, Yao B. Relationship between Helicobacter pylori infection and programmed death-ligand 1 in gastric cancer: A meta-analysis. World J Clin Oncol 2025; 16:102397. [PMID: 40290698 PMCID: PMC12019281 DOI: 10.5306/wjco.v16.i4.102397] [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: 10/16/2024] [Revised: 12/04/2024] [Accepted: 02/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignancies worldwide, and Helicobacter pylori (HP) infection is a well-established risk factor for its development. Programmed death-ligand 1 (PD-L1) expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment. While HP infection and PD-L1 expression in GC may be linked, the relationship between them remains unclear, in part because there have been conflicting results reported from various studies. AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC. METHODS A systematic literature review was conducted using PubMed, Embase, Cochrane Library, and Web of Science databases. Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included. Odds ratios and 95% confidence intervals were calculated to estimate the association. Heterogeneity was assessed using Cochrane's Q test and I² statistic. A random-effects model was used due to significant heterogeneity across studies. RESULTS Fourteen studies involving a total of 3069 patients with GC were included. The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues (odd ratio = 1.69, 95% confidence interval: 1.24-2.29, P < 0.001, I 2 = 59%). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses did not show significant variation based on geographic region, sample size, or method of PD-L1 assessment. Publication bias was minimal, as shown by funnel plots and Egger's regression test. CONCLUSION HP infection is associated with increased PD-L1 expression in GC, suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
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Affiliation(s)
- Hong-Chang Yang
- Department of Gastroenterology, Longgang Central Hospital of Shenzhen, Shenzhen 518100, Guangdong Province, China
| | - Cheng-Feng Fu
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Li-Jun Qiao
- Department of Basic Medical Sciences, Guizhou Health Vocational College, Tongren 554300, Guizhou Province, China
| | - Gen-He Long
- Department of School of Medicine, Guizhou Vocational and Technical College, Tongren 554300, Guizhou Province, China
| | - Li-Fen Yang
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Biao Yao
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
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Caspers IA, Slagter AE, Vissers PAJ, Lopez-Yurda M, Beerepoot LV, Ruurda JP, Nieuwenhuijzen GAP, Gisbertz SS, van Berge Henegouwen MI, Hartgrink HH, Goudkade D, Kodach LL, van Sandick JW, Verheij M, Verhoeven RHA, Cats A, van Grieken NCT. Histopathological response to chemotherapy and survival of mucinous type gastric cancer. J Natl Cancer Inst 2025; 117:253-261. [PMID: 39276158 PMCID: PMC11807439 DOI: 10.1093/jnci/djae227] [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: 04/10/2024] [Revised: 07/26/2024] [Accepted: 09/10/2024] [Indexed: 09/16/2024] Open
Abstract
BACKGROUND Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC), and diffuse (dif-GC) gastric cancer. METHODS Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery alone (SAvalidation) and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). RESULTS In the SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a 5-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, P = .52 and P = .011), but worse than int-GC (55% and 42%, P = .11 and P < .001). In the CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-) complete response) compared with int-GC (26% and 35%) and dif-GC (10% and 28%, P < .001 and P = .005). The 5-year RS in the CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared with dif-GC (35% and 38%, P = .004 and P < .001). CONCLUSION Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.
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Affiliation(s)
- Irene A Caspers
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
- Department of Pathology, Amsterdam University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Astrid E Slagter
- Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Pauline A J Vissers
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Martha Lopez-Yurda
- Department of Biometrics, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Laurens V Beerepoot
- Department of Oncology, Elisabeth Two Cities Hospital, Tilburg, the Netherlands
| | - Jelle P Ruurda
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | - Suzanne S Gisbertz
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Mark I van Berge Henegouwen
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Henk H Hartgrink
- Department of Surgical Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Danny Goudkade
- Department of Pathology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands
| | - Liudmila L Kodach
- Department of Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Johanna W van Sandick
- Department of Surgical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Marcel Verheij
- Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Rob H A Verhoeven
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Annemieke Cats
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, Amsterdam University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands
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Li Y, Sun W, Yuan S, Liu X, Zhang Z, Gu R, Li P, Gu X. The role of cuproptosis in gastric cancer. Front Immunol 2024; 15:1435651. [PMID: 39539553 PMCID: PMC11558255 DOI: 10.3389/fimmu.2024.1435651] [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: 05/20/2024] [Accepted: 08/19/2024] [Indexed: 11/16/2024] Open
Abstract
As a biologically essential transition metal, copper is widely involved in various enzymatic reactions and crucial biological processes in the body. It plays an increasingly important role in maintaining normal cellular metabolism and supporting the growth and development of the human body. As a trace element, copper maintains the dynamic balance of its concentration in body fluids through active homeostatic mechanisms. Both excess and deficiency of copper ions can impair cell function, ultimately leading to cell damage and death. Cuproptosis is a novel form of cell death where copper ions cause cell death by directly binding to the lipoylated components of the citric acid cycle (CAC) in mitochondrial respiration and interfering with the levels of iron-sulfur cluster (Fe-S cluster) proteins, ultimately causing protein toxic stress. Its primary characteristics are Cu2+ concentration dependence and high expression in mitochondrial respiratory cells. Recent research has revealed that, compared to other forms of programmed cell death such as apoptosis, necrosis, and autophagy, cuproptosis has unique morphological and biochemical features. Cuproptosis is associated with the occurrence and development of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. This article focuses on a review of the relevance of cuproptosis in gastric cancer (GC).
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Affiliation(s)
- Yixian Li
- Nanjing University of Chinese Medicine, the First Clinical Medical College, Nanjing, Jiangsu, China
| | - Wenhao Sun
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Shaolin Yuan
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Xinxin Liu
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province, Nanjing, Jiangsu, China
| | - Ziqi Zhang
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Renjun Gu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Pengfei Li
- Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xin Gu
- School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Ma Y, Zhang S, Wang Y, Hu C, Chen J, Pang C, Liang C, Yuan L, Du Y. Comparison of Clinicopathological Features and Prognosis of Mucinous Gastric Carcinoma and other Gastric Cancers: A Retrospective Study of 4,417 Patients. J Gastrointest Surg 2023; 27:2352-2364. [PMID: 37848685 DOI: 10.1007/s11605-023-05853-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: 06/28/2023] [Accepted: 09/29/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND Mucinous gastric carcinoma (MGC) is a distinct histologic subtype of gastric cancer (GC) that is often diagnosed at an advanced stage. The clinicopathological characteristics and prognosis of MGC, when compared to adenocarcinoma and signet-ring cell carcinoma (SRCC), are currently subjects of debate and require further investigation. METHODS In this study, we conducted an investigation on 4,417 patients who were hospitalized with GC at Zhejiang Cancer Hospital between April 2008 and December 2019. The objective was to compare the prognosis and clinicopathological characteristics of MGC with other types of GC. RESULTS In comparison to adenocarcinoma, MGC patients exhibited more advanced tumor infiltration (p < 0.001), lower tumor differentiation (p < 0.001), and higher rates of preoperative tumor marker positivity (except for AFP and CA125) (all p < 0.05). However, after propensity score matching (PSM) to eliminate confounding factors, MGC patients surprisingly exhibited a better prognosis than adenocarcinoma patients (p = 0.008), and the results in multifactorial COX regression were similar (HR = 0.792, 95% CI 0.629-0.997, p = 0.047). Among patients with MGC, age, pN stage, as well as preoperative levels of CA125 and CA724 (all p < 0.05), emerged as independent prognostic markers. While overall survival did not significantly differ between MGC and SRCC (p = 0.196), significant survival disparities emerged in advanced-stage patients (p = 0.009), with MGC showing better survival rates. Furthermore, a nomogram was developed to predict 1-, 3-, and 5-year survival in gastric cancer patients based on various factors, achieving a C-index of 0.772 (95% CI: 0.745-0.799). CONCLUSIONS While the poorer prognosis associated with MGC may be linked to its advanced stage and lower degree of differentiation, its biological behavior could contribute to improved survival.
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Affiliation(s)
- Yubo Ma
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Shengjie Zhang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Yi Wang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Can Hu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
| | - Jinxia Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Chuhong Pang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Chen Liang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Li Yuan
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
| | - Yian Du
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
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Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, Feng T, Cui Z, Zhu T, Li Y, Qiu Z, Fan G, Huang C. Lactylation of METTL16 promotes cuproptosis via m 6A-modification on FDX1 mRNA in gastric cancer. Nat Commun 2023; 14:6523. [PMID: 37863889 PMCID: PMC10589265 DOI: 10.1038/s41467-023-42025-8] [Citation(s) in RCA: 151] [Impact Index Per Article: 75.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 09/27/2023] [Indexed: 10/22/2023] Open
Abstract
Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore- elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.
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Affiliation(s)
- Lianhui Sun
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
- Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Yuan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Boyu Yang
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Sijun Sun
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Pengshan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Zai Luo
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Tingting Feng
- Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Zelin Cui
- Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Ting Zhu
- Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Yuming Li
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Zhengjun Qiu
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China
| | - Guangjian Fan
- Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
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Zhu Y, Zhu F, Ba H, Chen J, Bian X. Helicobacter pylori infection and PD-L1 expression in gastric cancer: A meta-analysis. Eur J Clin Invest 2023; 53:e13880. [PMID: 36164962 DOI: 10.1111/eci.13880] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC. METHODS Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. RESULTS Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I2 = 53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04). CONCLUSION Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.
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Affiliation(s)
- Yaodong Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Fangyuan Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - He Ba
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Jie Chen
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Xiuliang Bian
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
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Meagher NS, Hamilton P, Milne K, Thornton S, Harris B, Weir A, Alsop J, Bisinoto C, Brenton JD, Brooks-Wilson A, Chiu DS, Cushing-Haugen KL, Fereday S, Garsed DW, Gayther SA, Gentry-Maharaj A, Gilks B, Jimenez-Linan M, Kennedy CJ, Le ND, Piskorz AM, Riggan MJ, Shah M, Singh N, Talhouk A, Widschwendter M, Bowtell DDL, Candido Dos Reis FJ, Cook LS, Fortner RT, García MJ, Harris HR, Huntsman DG, Karnezis AN, Köbel M, Menon U, Pharoah PDP, Doherty JA, Anglesio MS, Pike MC, Pearce CL, Friedlander ML, DeFazio A, Nelson BH, Ramus SJ. Profiling the immune landscape in mucinous ovarian carcinoma. Gynecol Oncol 2023; 168:23-31. [PMID: 36368129 PMCID: PMC10374276 DOI: 10.1016/j.ygyno.2022.10.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.
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Affiliation(s)
- Nicola S Meagher
- School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia; The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council New South Wales, Australia.
| | - Phineas Hamilton
- Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
| | - Katy Milne
- Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
| | - Shelby Thornton
- Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
| | - Bronwyn Harris
- Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
| | - Ashley Weir
- School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
| | - Jennifer Alsop
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Christiani Bisinoto
- Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - James D Brenton
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | | | - Derek S Chiu
- British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada
| | - Kara L Cushing-Haugen
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Sian Fereday
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
| | - Dale W Garsed
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
| | - Simon A Gayther
- Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK
| | - Blake Gilks
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
| | | | - Catherine J Kennedy
- Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia
| | - Nhu D Le
- Cancer Control Research, BC Cancer, Vancouver, BC, Canada
| | - Anna M Piskorz
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Marjorie J Riggan
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA
| | - Mitul Shah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Naveena Singh
- Department of Pathology, Barts Health National Health Service Trust, London, UK; Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, Canada
| | - Aline Talhouk
- British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
| | | | - David D L Bowtell
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
| | - Francisco J Candido Dos Reis
- Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
| | - Linda S Cook
- Epidemiology, School of Public Health, University of Colorado, Aurora, CO, USA; Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Renée T Fortner
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - María J García
- Computational Oncology Group, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | - Holly R Harris
- Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - David G Huntsman
- Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada
| | - Anthony N Karnezis
- Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA, USA
| | - Martin Köbel
- Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada
| | - Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK
| | - Paul D P Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
| | - Jennifer A Doherty
- Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Michael S Anglesio
- British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, BC, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
| | - Malcolm C Pike
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Population Health and Public Health Sciences, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Celeste Leigh Pearce
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Michael L Friedlander
- School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia; Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, New South Wales, Australia
| | - Anna DeFazio
- The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council New South Wales, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; The University of Sydney, Sydney, New South Wales, Australia
| | - Brad H Nelson
- Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada
| | - Susan J Ramus
- School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.
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Predicting Overall Survival in Patients with Nonmetastatic Gastric Signet Ring Cell Carcinoma: A Machine Learning Approach. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:4862376. [PMID: 36148015 PMCID: PMC9489421 DOI: 10.1155/2022/4862376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/30/2022]
Abstract
Background and Aims Accurate prediction is essential for the survival of patients with nonmetastatic gastric signet ring cell carcinoma (GSRC) and medical decision-making. Current models rely on prespecified variables, limiting their performance and not being suitable for individual patients. Our study is aimed at developing a more precise model for predicting 1-, 3-, and 5-year overall survival (OS) in patients with nonmetastatic GSRC based on a machine learning approach. Methods We selected 2127 GSRC patients diagnosed from 2004 to 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly partitioned them into a training and validation cohort. We compared the performance of several machine learning-based models and finally chose the eXtreme gradient boosting (XGBoost) model as the optimal method to predict the OS in patients with nonmetastatic GSRC. The model was assessed using the receiver operating characteristic curve (ROC). Results In the training cohort, for predicting OS rates at 1-, 3-, and 5-year, the AUCs of the XGBoost model were 0.842, 0.831, and 0.838, respectively, while in the testing cohort, the AUCs of 1-, 3-, and 5-year OS rates were 0.749, 0.823, and 0.829, respectively. Besides, the XGBoost model also performed better when compared with the American Joint Committee on Cancer (AJCC) stage. The performance for this model was stably maintained when stratified by age and ethnicity. Conclusion The XGBoost-based model accurately predicts the 1-, 3-, and 5-year OS in patients with nonmetastatic GSRC. Machine learning is a promising way to predict the survival outcomes of tumor patients.
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Wang PH, Huo TI. Outstanding research paper awards of the Journal of the Chinese Medical Association in 2020. J Chin Med Assoc 2021; 84:1071-1072. [PMID: 34670226 DOI: 10.1097/jcma.0000000000000639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Peng-Hui Wang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Female Cancer Foundation, Taipei, Taiwan, ROC
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, ROC
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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Controlling Nutritional Status (CONUT) Score Is a Prognostic Factor for Patients with Gastric Cancer Treated by Perioperative FLOT. J Gastrointest Cancer 2021; 53:571-580. [PMID: 34263428 DOI: 10.1007/s12029-021-00664-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE The aim of this study was to show that the Controlling Nutritional Status (CONUT) score has predictive value in gastric cancer (GC) patients treated with perioperative fluorouracil, leucovorin, oxaliplatin, or docetaxel (FLOT). METHODS A total of 161 GC patients treated with perioperative FLOT in our center were included in the study. The ideal cutoff values for the CONUT score were obtained using the receiver operating characteristic (ROC) curve analysis, and the patients were divided into low (≤3) and high (> 3) CONUT groups. The associations of CONUT with clinicopathological factors and survival were evaluated retrospectively. RESULTS The median follow-up time was 11.2 months (2.3-32.3 months). The median overall survival (OS) for the entire population was 14.7 months (95% CI 13.5-15.9 months). Median OS was not reached in the low-CONUT group, but it was 14.2 months (95% CI 12.6-15.9) in the high-CONUT group and the difference was statistically significant (p = 0.002). The univariate Cox proportional hazards model revealed that OS was significantly associated with Eastern Cooperative Oncology Group (ECOG) status (p < 0.001), T4b stage (p 0.03), modified Glasgow Prognostic Scores (mGPS) (p 0.005), prognostic index (PI) (p 0.011), prognostic nutritional index (PNI) (p < 0.001), CONUT score (p 0.003), and mucinous histology (p 0.004). In multivariate analysis, ECOG performance status (p 0.029), PNI (p 0.001), CONUT score (p 0.040), and mucinous histology (p 0.001) were still identified as independent prognostic factors for OS. CONCLUSIONS Our study demonstrated the prognostic significance of the CONUT score in GC patients treated with perioperative FLOT.
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Prognostic analysis of gastric signet ring cell carcinoma and mucinous carcinoma: a propensity score-matched study and competing risk analysis. Aging (Albany NY) 2020; 12:22059-22077. [PMID: 33130635 PMCID: PMC7695374 DOI: 10.18632/aging.104048] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 08/31/2020] [Indexed: 12/11/2022]
Abstract
Background: Limited evidence and contradictory results have been reported regarding the impact of signet ring cell carcinoma (SRC) and mucinous gastric cancer (MGC) classifications on the prognosis of gastric cancer (GC). Results: Information on 6017 patients and 266 patients was extracted from the SEER database and our hospital records, respectively. We found that patients with MGC had a better survival rate than those with SRC (P=0.012), but in the early stage, MGC was a risk factor for a poor prognosis. After PSM, for both patients from the SEER database and our hospital, the prognosis of patients with SRC was poorer than that of patients with MGC (P<0.05), but patients with MGC in early-stage GC showed poorer survival. Additionally, SRC was demonstrated to be a risk factor in the multivariate competing risk regression model for cancer-specific survival. Conclusion: Patients with SRC may have a worse prognosis than those with MGC, but for early-stage GC, patients with SRC have a better prognosis than those with MGC. Method: Patients from the SEER database and from our hospital diagnosed with SRC or MGC were included in a Cox regression analysis, multivariate competing risk model and propensity score matching (PSM) analysis.
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Chen MH, Fang WL, Hung YP, Chao Y. Mucinous gastric adenocarcinoma: A good candidate for immune therapy? J Chin Med Assoc 2020; 83:624-625. [PMID: 32332521 DOI: 10.1097/jcma.0000000000000329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Affiliation(s)
- Ming-Huang Chen
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Wen-Liang Fang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Ping Hung
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yee Chao
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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Huang CY, Cheng NM, Wang PH. Risk factors associated with epithelial ovarian cancer in women with endometriosis. Taiwan J Obstet Gynecol 2020; 59:353-355. [DOI: 10.1016/j.tjog.2020.03.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2020] [Indexed: 12/12/2022] Open
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