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Ma W, Guo H, Yang P, He J, Li T, Wu H, Wu J, Yang J, Tian Y, Guo S, Wang G, Wang H, Wang Q, Er L, Ding P, Zhao Q. Lymph node metastasis mapping and prognostic analysis of early gastric cancer. J Gastrointest Surg 2025; 29:102082. [PMID: 40381833 DOI: 10.1016/j.gassur.2025.102082] [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: 01/16/2025] [Revised: 04/01/2025] [Accepted: 05/09/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND Currently, numerous studies focus on the analysis of risk factors for lymph node metastasis in early gastric cancer, but few studies analyze the drainage patterns of metastatic lymph nodes. METHODS Data were retrospectively analyzed from a database of gastric cancer resections from 2014 to 2018. The cohort included 786 pT1 patients with complete data. Outcomes evaluated were lymph node metastasis frequencies, survival analyses, and risk factors affecting prognosis. RESULTS The overall lymph node metastasis rate was 23.7%. The 5-year overall survival (OS) rate (54.8% vs 95.7%; P <.001) and disease-free survival (DFS) rate (48.4% vs 95.7%; P <.001) of patients with node-positive disease were significantly worse than those of patients with node-negative disease. Multivariable Cox regression identified tumor size of >2 cm (P =.007; P <.001), poor differentiation (P =.007; P <.001), T1b stage (all P <.001), lymph node metastasis (all P <.001), and vascular invasion (all P =.002; P =.016) as independent negative prognostic factors affecting 5-year OS and DFS in patients with early gastric cancer. Postoperative chemotherapy (P <.001; P =.019) was an independent positive prognostic factor. CONCLUSION This real-world observational study demonstrates that lymph node metastasis in early gastric cancer is widely and disorderly not depending on the location. Therefore, systematic lymph node dissection is necessary to cure early gastric cancer. Meanwhile, its prognosis is closely related to lymph node metastasis.
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Affiliation(s)
- Wenqian Ma
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Honghai Guo
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Peigang Yang
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Jinchen He
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Tongkun Li
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Haotian Wu
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Jiaxiang Wu
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Jiaxuan Yang
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Yuan Tian
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China
| | - Shuo Guo
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Gongning Wang
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hongcai Wang
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qi Wang
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Limian Er
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China; Department of Endoscopy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ping'an Ding
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China.
| | - Qun Zhao
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China; Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China; Big data analysis and mining application for precise diagnosis and treatment of gastric cancer, Hebei Provincial Engineering Research Center, Shijiazhuang, China.
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Saha S, Bapat S, Vijayasarathi D, Vyas R. Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies. Mol Divers 2025; 29:2341-2366. [PMID: 39348085 DOI: 10.1007/s11030-024-10995-6] [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: 07/10/2024] [Accepted: 09/15/2024] [Indexed: 10/01/2024]
Abstract
Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.
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Affiliation(s)
- Sagarika Saha
- MIT ADTU School of Bioengineering Sciences & Research, MIT Art, Design and Technology University, Pune, Maharashtra, India
| | - Sanket Bapat
- MIT ADTU School of Bioengineering Sciences & Research, MIT Art, Design and Technology University, Pune, Maharashtra, India
| | - Durairaj Vijayasarathi
- MIT ADTU School of Bioengineering Sciences & Research, MIT Art, Design and Technology University, Pune, Maharashtra, India
| | - Renu Vyas
- MIT ADTU School of Bioengineering Sciences & Research, MIT Art, Design and Technology University, Pune, Maharashtra, India.
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Niu C, Song Y, Chen Y, Shi Y, Wang H, Wu X, Wang X, Zhao X, Bu Y, Li J, Tao T, Wu J, Xue C, Zhang F, Han C, Yuan J, Zhang Q. Epidemiology of Helicobacter pylori, gastric precancerous lesions and gastric cancer: a multicenter, population-based cross-sectional study in Nanjing. BMC Infect Dis 2025; 25:766. [PMID: 40426075 PMCID: PMC12117699 DOI: 10.1186/s12879-025-11147-3] [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: 09/05/2024] [Accepted: 05/20/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Nanjing City has a high-incidence gastric cancer (GC), but the epidemiology of gastric precancerous lesions (GPLs) remains poorly understood. This study aimed to investigate the epidemiological characteristics of Helicobacter pylori (H. pylori) infection, GPLs, and GCs in patients undergoing endoscopic examination in Lishui District, Nanjing. METHODS This retrospective, population-based, cross-sectional study was conducted collaboratively by the Nanjing Lishui People's Hospital and six medical community units within the county between July 2022 and June 2023. Data on biopsies and 13C urea breath tests (13C-UBT) were collected. RESULTS A total of 15,668 individuals were included, among whom 259 had GPL (1.65%) and 218 had GC (1.39%). The H. pylori infection rate in total patients was 5014 (32.00%) (males: 2684 (34.06%); females: 2335 (29.92%)). The H. pylori infection rate is 31.45% in benign gastric lesions, 44.40% in GPLs, and 55.50% in GC, respectively. The multivariable logistic regression analysis showed that male (OR = 3.156, 95% CI: 2.865-3.376, P < 0.001), age (OR = 1.785, 95% CI: 1.703-1.876, P < 0.001), fresh vegetable, fruit, and white meat intake frequently (OR = 0.865, 95% CI: 0.506-2.061, P = 0.029), high-salt diet and high-fat diet intake frequently (OR = 1.906, 95% CI: 1.101-2.932, P = 0.014), rural residence (OR = 2.682, 95% CI: 1.010-4.754, P = 0.040), H. pylori infection (OR = 2.022, 95% CI: 1.155-2.865, P < 0.001) and atrophic gastritis and/or intestinal metaplasia (OR = 4.875, 95% CI: 2.229-10.663, P < 0.001) were associated with GPLs. Male (OR = 2.021, 95% CI: 1.080-3.780, P = 2.028), age (OR = 1.201, 95% CI: 1.174-1.238, P < 0.001), digestive symptoms (OR = 2.256, 95% CI: 1.548-3.289, P < 0.001), bachelor degree below (OR = 4.792, 95% CI: 3.439-6.837, P < 0.001), farmer (OR = 1.039, 95% CI: 1.026-1.159, P < 0.001), fresh vegetable, fruit, and white meat intake (OR = 0.231, 95% CI: 0.141-0.379, P < 0.001), fried/barbecue/pickled food intake (OR = 6.781, 95% CI: 3.783-12.153, P < 0.001), high-salt diet and high-fat diet intake (OR = 4.374, 95% CI: 2.363-8.097, P < 0.001), rural residence (OR = 1.230, 95% CI: 1.121-1.437, P < 0.001), H. pylori infection (OR = 3.248, 95% CI: 2.357-4.477, P < 0.001) and atrophic gastritis and/or intestinal metaplasia (OR = 4.875, 95% CI: 2.636-9.016, P < 0.001) were associated with GCs. CONCLUSIONS These findings underscore the importance of implementing targeted prevention strategies and early detection programs in high-risk populations to mitigate the burden of GPLs and GCs in Nanjing.
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Affiliation(s)
- Chunyan Niu
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China.
| | - Yongqiang Song
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yue Chen
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yongqiang Shi
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Hui Wang
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xinguo Wu
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xiaoping Wang
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xiangyang Zhao
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yongdan Bu
- Dongping Street Health Center in Nanjing Lishui District, Nanjing, 211212, China
| | - Jijin Li
- Jingqiao Central Health Center in Nanjing Lishui District, Nanjing, 211224, China
| | - Tao Tao
- Honglan Street Health Center in Nanjing Lishui District, Nanjing, 211219, China
| | - Jinhua Wu
- Shiqiu Central Health Center in Nanjing Lishui District, Nanjing, 211222, China
| | - Changlin Xue
- Baima Central Health Center in Nanjing Lishui District, Nanjing, 211225, China
| | - Fuyu Zhang
- Yongyang Street Community Health Service Center in Nanjing Lishui District, Nanjing, 211299, China
| | - Chunrong Han
- Department of Pathology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Juan Yuan
- Department of Pathology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Qiang Zhang
- Department of Gastroenterology, Yancheng Third People's Hospital (The Yancheng School of Clinical Medicine of Nanjing Medical University), Yancheng, 224000, China.
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Wu Y, Liu J, Yin T, Li X, Liu X, Peng X, Zhan X. SELP can affect the immune microenvironment of gastric cancer and is associated with poor prognosis. Discov Oncol 2025; 16:846. [PMID: 40397261 PMCID: PMC12095770 DOI: 10.1007/s12672-025-02629-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 05/08/2025] [Indexed: 05/22/2025] Open
Abstract
The tumor microenvironment (TME) plays a crucial role in the occurrence and progression of gastric cancer. Yet, we still don't understand how immune and stromal components of TMEs are modulated. In this study, we applied the ESTIMATE algorithm to calculate the number of immune and stromal components in 410 STAD cases in the Cancer Genome Atlas (TCGA) database. COX regression analysis and protein-protein interaction (PPI) network construction were used to analyze differentially expressed genes (DEGs). Then, P-selectin (SELP) was identified as a predictor by cross-analysis of univariate COX and PPI. After verifying the clinical significance of SELP for study, we performed an immune infiltration analysis and identified 54 immunomodulators associated with SELP through public data. Immunomodulation associated with gastric cancer prognosis was then confirmed by LASSO regression, and the previous results were further validated with single-cell data. Finally, we verified that SELP can promote EMT on gastric cancer cells. In conclusion, we validated that SELP may affect the biological phenotype of gastric cancer with the immune microenvironment alteration of gastric cancer.
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Affiliation(s)
- Yue Wu
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China
| | - Jingyu Liu
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China
| | - Tong Yin
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China
| | - Xiaoxiao Li
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China
| | - Xian Liu
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China
| | - Xiaobo Peng
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China.
| | - Xianbao Zhan
- Department of Oncology, Changhai Hospital, Naval Military Medical University, Shanghai, 200433, China.
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Meng FD, Jia SM, Ma YB, Du YH, Liu WJ, Yang Y, Yuan L, Nan Y. Identification of key hub genes associated with anti-gastric cancer effects of lotus plumule based on machine learning algorithms. World J Gastrointest Oncol 2025; 17:103048. [PMID: 40235894 PMCID: PMC11995348 DOI: 10.4251/wjgo.v17.i4.103048] [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: 11/07/2024] [Revised: 12/11/2024] [Accepted: 01/16/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Lotus plumule and its active components have demonstrated inhibitory effects on gastric cancer (GC). However, the molecular mechanism of lotus plumule against GC remains unclear and requires further investigation. AIM To identify the key hub genes associated with the anti-GC effects of lotus plumule. METHODS This study investigated the potential targets of traditional Chinese medicine for inhibiting GC using weighted gene co-expression network analysis and bioinformatics. Initially, the active components and targets of the lotus plumule and the differentially expressed genes associated with GC were identified. Subsequently, a protein-protein interaction network was constructed to elucidate the interactions between drug targets and disease-related genes, facilitating the identification of hub genes within the network. The clinical significance of these hub genes was evaluated, and their upstream transcription factors and downstream targets were identified. The binding ability of a hub gene with its downstream targets was verified using molecular docking technology. Finally, molecular docking was performed to evaluate the binding affinity between the active ingredients of lotus plumule and the hub gene. RESULTS This study identified 26 genes closely associated with GC. Machine learning analysis and external validation narrowed the list to four genes: Aldo-keto reductase family 1 member B10, fructose-bisphosphatase 1, protein arginine methyltransferase 1, and carbonic anhydrase 9. These genes indicated a strong correlation with anti-GC activity. CONCLUSION Lotus plumule exhibits anti-GC effects. This study identified four hub genes with potential as novel targets for diagnosing and treating GC, providing innovative perspectives for its clinical management.
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Affiliation(s)
- Fan-Di Meng
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shu-Min Jia
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yu-Bin Ma
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yu-Hua Du
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Wen-Jing Liu
- Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Yang
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Ling Yuan
- College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Yi Nan
- Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
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Wei W, Li J, Huang J, Jiang Q, Lin C, Hu R, Wei J, Li Q, Xu G, Chang Z. Exosomal miR‑3681‑3p from M2‑polarized macrophages confers cisplatin resistance to gastric cancer cells by targeting MLH1. Mol Med Rep 2025; 31:94. [PMID: 39981936 PMCID: PMC11851060 DOI: 10.3892/mmr.2025.13459] [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: 08/12/2024] [Accepted: 01/07/2025] [Indexed: 02/22/2025] Open
Abstract
Cisplatin (DDP) is a key chemotherapeutic agent in the treatment of gastric cancer; however, its efficacy is often limited by chemoresistance, a notable challenge in clinical oncology. The present study aimed to investigate the influence of exosomes derived from M2‑polarized macrophages, which promote this resistance, on the response of gastric cancer cells to DDP, examining both the effects and the underlying mechanisms. M2 macrophages, differentiated from mouse bone marrow cells with interleukin (IL)‑13 and IL‑4, were identified using immunofluorescence staining for CD206 and CD163. Exosomes derived from these macrophages were characterized using transmission electron microscopy and protein markers, including calnexin, tumor susceptibility gene 101 and CD9. The role of exosomal microRNA (miR)‑3681‑3p in DDP resistance was assessed using Cell Counting Kit‑8 and apoptosis assays, while a luciferase reporter assay was used to elucidate the interaction between miR‑3681‑3p and MutL protein homolog 1 (MLH1). Co‑culturing gastric cancer cells with M2 macrophages enhanced DDP resistance, an effect amplified by exosomes from M2 macrophages enriched with miR‑3681‑3p. This microRNA directly targeted and reduced MLH1 protein expression. Overexpression of miR‑3681‑3p through mimic transfection, along with MLH1 silencing by small interfering RNA transfection, significantly increased DDP resistance, as evidenced by elevated IC50 values in AGS cells. By contrast, the overexpression of MLH1 effectively reversed the drug resistance of AGS cells to DDP caused by miR‑3681‑3p mimic transfection, as evidenced by a decrease in the IC50 value. In conclusion, exosomal miR‑3681‑3p from M2 macrophages may have a key role in conferring DDP resistance to gastric cancer by suppressing MLH1, offering a new therapeutic target for overcoming chemoresistance.
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Affiliation(s)
- Wujun Wei
- Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
- Clinic Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
- Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
- Baise Key Laboratory for Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Jiaxing Li
- Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Jingjing Huang
- Department of Health Care, Baise Maternity and Child Health Center, Baise, Guangxi 533000, P.R. China
| | - Qi Jiang
- Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Cheng Lin
- Department of Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Rentong Hu
- Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Jiazhu Wei
- Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Qiao Li
- Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Guidan Xu
- Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
| | - Zhengyi Chang
- Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
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Shi X, Shi X, Yan Y, Gong A. Modified Charlson comorbidity index of long-term, non-gastric cancer mortality in patients with early gastric cancer: a multicenter retrospective study. World J Surg Oncol 2025; 23:100. [PMID: 40128794 PMCID: PMC11931881 DOI: 10.1186/s12957-025-03741-1] [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: 12/12/2024] [Accepted: 03/07/2025] [Indexed: 03/26/2025] Open
Abstract
PURPOSE In patients with early gastric cancer (EGC) who undergo endoscopic submucosal dissection (ESD) with endoscopic curability (eCura) C-2, the risk of non-gastric cancer mortality should be evaluated before receiving further gastrectomy. Charlson comorbidity index (CCI) is often used to estimate prognosis based on patient's background before treatment. We identified the long-term risk of mortality from other causes associated with comorbidities in CCI and applied it to the creation of EGC specific CCI (GCCI). METHODS A total of 1810 patients with EGC from 3 centers were included from January 2015 to February 2023. We used Cox proportional risk models to determine the risk of non-gastric cancer mortality related to comorbidities and used these hazard ratios to reweight the Charlson index to establish GCCI. RESULTS The Cox model suggested that moderate to severe liver disease, metastatic solid tumors, severe to very severe chronic obstructive pulmonary disease (COPD), and leukemia had the highest risk of non-gastric cancer mortality [hazard ratio (HR) > 5)]. Survival analysis showed that the 5-year non-gastric cancer mortality rates in low-risk group (GCCI score 0-1), medium-risk group (GCCI score 2-4), and high-risk group (GCCI score 5-13) were 3%, 10%, and 52%, respectively. CONCLUSIONS GCCI could identify patients with EGC who have higher non-gastric cancer mortality. The GCCI could be used to help patients with EGC make medical decisions.
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Affiliation(s)
- Xiao Shi
- Department of Gastroenterology, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Xiaoyi Shi
- Department of Gastroenterology, First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Yuxing Yan
- Department of Gastroenterology, the Second People's Hospital of Liaocheng, Liaocheng, China
| | - Aixia Gong
- Department of Gastroenterology, First Affiliated Hospital, Dalian Medical University, Dalian, China.
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Wu HM, Ying XX, Lv LL, Hu JW. Diagnostic implications of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammatory index for gastric carcinoma. World J Gastrointest Surg 2025; 17:100130. [PMID: 39872777 PMCID: PMC11757178 DOI: 10.4240/wjgs.v17.i1.100130] [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: 08/20/2024] [Revised: 09/19/2024] [Accepted: 09/27/2024] [Indexed: 12/27/2024] Open
Abstract
BACKGROUND The diagnosis of gastric carcinoma (GC) is essential for improving clinical outcomes. However, the biomarkers currently used for GC screening are not ideal. AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) for GC. METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed. The information on peripheral blood platelet, neutrophil, and lymphocyte counts in each patient was collected, and the NLR, PLR, and SII levels of both groups were calculated. Additionally, multivariate logistic regression analysis was conducted, and the diagnostic implications of NLR, PLR, and SII in differentiating patients with precancerous gastric conditions, compared with those with GC, were analyzed through receiver operating characteristic (ROC) curves. RESULTS The data indicated that NLR, PLR, and SII had abnormally increased levels in the patients with GC. Gender and body mass index were risk factors for the occurrence of GC. ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions, who were differentiated from those with GC, were 0.824, 0.787, and 0.842, respectively. CONCLUSION NLR, PLR, and SII are all abnormally expressed in GC and have diagnostic implications, especially when used as joint indicators, in distinguishing patients with precancerous gastric conditions from those with GC.
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Affiliation(s)
- Huang-Min Wu
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Xiao-Xuan Ying
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Li-Li Lv
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Jian-Wen Hu
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
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9
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Kim SD, Pyo SJ, Kim DH, Yoo HS, Park SJ. Efficacy and safety of herbal medicine treatment on postsurgical recovery in gastric cancer patients: A systematic review and meta-analysis. Medicine (Baltimore) 2025; 104:e41034. [PMID: 40184097 PMCID: PMC11709200 DOI: 10.1097/md.0000000000041034] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/24/2024] [Accepted: 12/03/2024] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is the second most prevalent cancer in Korea, and is associated with significant morbidity and mortality. Although advancements in early detection and treatment have improved survival rates, management of postsurgical recovery remains vital. Herbal medicine (HM) has emerged as a potential adjunct therapy for enhancing the recovery and quality of life (QoL) of patients post-GC surgery. METHODS This systematic review and meta-analysis evaluated the efficacy and safety of HM in the postsurgical recovery of patients with GC. We searched both Korean and international databases and identified 16 randomized controlled trials that met our inclusion criteria. We assessed the study quality using the Cochrane Risk of Bias tool and analyzed the data using the Review Manager Software (RevMan). RESULTS Our analysis included 1546 patients from selected studies, demonstrating that HM significantly improved gastrointestinal recovery times, including the time to first flatus, bowel movement, and return of bowel sounds. Significant improvements were also observed in nutritional markers, such as albumin and prealbumin, along with beneficial effects on immune markers, such as CD3+ and CD4+ levels. QoL assessments using the WHOQOL-BREF and QLQ-C30 indicated substantial improvements. HM had a favorable safety profile, showing a reduced incidence of adverse effects compared to the controls. CONCLUSION The findings suggest that HM can significantly enhance recovery and improve quality of life following GC surgery, with a favorable safety profile. However, due to the considerable heterogeneity in study results, extended clinical trials and rigorous follow-ups are recommended to comprehensively assess long-term effects and side effects.
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Affiliation(s)
- Soo-Dam Kim
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Sook-Jin Pyo
- East-West Cancer Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, Republic of Korea
| | - Dong-Hyeon Kim
- Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea
| | - Hwa-Seung Yoo
- East-West Cancer Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, Republic of Korea
| | - So-Jung Park
- Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea
- Department of Korean Internal Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea
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10
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Xiang Y, Yao LD. Risk factors for lymph node metastasis and invasion depth in early gastric cancer: Analysis of 210 cases. World J Gastrointest Surg 2024; 16:3720-3728. [PMID: 39734454 PMCID: PMC11650229 DOI: 10.4240/wjgs.v16.i12.3720] [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: 06/20/2024] [Revised: 09/25/2024] [Accepted: 10/23/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Gastric cancer is the leading cause of cancer-related deaths worldwide. Early gastric cancer (EGC) is often associated with the risk of lymph node metastasis, which influences treatment decisions. Despite the use of enhanced computed tomography, the prediction of lymph node involvement remains challenging. AIM To investigate the risk factors for lymph node metastasis and invasion depth in patients with EGC. METHODS In total, 210 patients with pathologically diagnosed EGC were included in this study. Univariate and multivariate statistical analyses were used to predict risk factors for lymph node metastasis and invasion depth in patients with EGC. RESULTS Among the 210 patients, 27 (12.9%) had lymph node metastases. Of the 117 patients with submucosal gastric cancer, 24 (20.5%) had lymph node metastases. Both univariate and multivariate analyses indicated that the depth of invasion in EGC was a risk factor for lymph node metastasis in these patients. Additionally, pathological type was identified as a risk factor for cancer cell invasion in patients with EGC. CONCLUSION EGC invasion depth, not tumor type, size, age, sex, or location, predicts lymph node spread. Tumor type, not size, age, sex, or location, predicts cancer cell invasion.
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Affiliation(s)
- Yu Xiang
- Department of Gastroenterology, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
| | - Li-Di Yao
- Department of Radiology, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
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11
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Han X, Yu W. Value of serum pepsinogen ratio screening for early gastric cancer and precancerous lesions in Youcheng area. World J Gastrointest Surg 2024; 16:3729-3736. [PMID: 39734444 PMCID: PMC11650226 DOI: 10.4240/wjgs.v16.i12.3729] [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: 08/28/2024] [Revised: 10/16/2024] [Accepted: 10/28/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND The 5-year survival rate of patients with advanced gastric cancer remains extremely low (< 15%), whereas the 5-year survival rate of patients with early gastric cancer (EGC) is > 90%. Consequently, strengthening the screening of patients with EGC and precancerous lesions (PCLs) is essential. AIM To identify the value of serum pepsinogen ratio (PGR) screening for EGC and PCLs in the Shengli Oilfield Central Hospital. METHODS We first selected 385 patients with gastric lesions in the Youcheng area, determining benign lesions, PCLs, and EGC in 135, 123, and 127 cases, respectively, based on endoscopy and case diagnosis. The positive rates of pepsinogen I, pepsinogen II and Helicobacter pylori (H. pylori) in the three groups were detected, and the PGR was calculated. Subsequently, we plotted receiver operating characteristic curves to analyze the screening value of PGR and H. pylori-positive rates for PCLs and EGC. RESULTS PGR expression demonstrated a decreasing trend in patients with benign lesions, PCLs, and EGC successively according to the detection results, whereas the H. pylori-positive rate was notably increased in patients with PCLs and EGC compared to those with benign lesions. The area under the curves (AUCs) of PGR, H. pylori, and their combination in differentiating patients with benign lesions from those with PCLs were 0.611, 0.582, and 0.689, respectively; PGR, H. pylori, and their combination had an AUC of 0.618, 0.502, and 0.618 in distinguishing PCL patients from EGC patients, respectively; the AUCs of PGR, H. pylori, and their combination in discriminating patients with benign lesions from those with EGC were 0.708, 0.581, and 0.750, respectively. CONCLUSION PGR has great screening potential for patients with EGC and PCLs in the Youcheng area, and the screening efficiency is further improved by combining the H. pylori-positive rate.
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Affiliation(s)
- Xue Han
- Department of General Practice, Shengli Oilfield Central Hospital, Dongying 257000, Shandong Province, China
| | - Wei Yu
- Health Management Center, Shengli Oilfield Central Hospital, Dongying 257000, Shandong Province, China
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12
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Yuan W, Shi Y, Dai S, Deng M, Zhu K, Xu Y, Chen Z, Xu Z, Zhang T, Liang S. The role of MAPK pathway in gastric cancer: unveiling molecular crosstalk and therapeutic prospects. J Transl Med 2024; 22:1142. [PMID: 39719645 PMCID: PMC11667996 DOI: 10.1186/s12967-024-05998-8] [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: 09/22/2024] [Accepted: 12/15/2024] [Indexed: 12/26/2024] Open
Abstract
Gastric cancer remains a significant health burden globally, especially prevalent in Asian and European regions. Despite a notable decline in incidence in the United States and Western Europe over recent decades, the disease's persistence underscores the urgency for advanced research in its pathogenesis and treatment strategies. Central to this pursuit is the exploration of the mitogen-activated protein kinase (MAPK) pathway, a pivotal cellular mechanism implicated in the complex processes of gastric cancer development, including cellular proliferation, invasion, migration, and metastasis. The MAPK or extracellular signal-regulated kinase pathway serves as a crucial conduit for transmitting extracellular signals to elicit intracellular responses, with its signaling cascades subject to alterations due to genetic and epigenetic variations across various diseases, prominently cancer. This review delves into the intricate role of the MAPK signaling pathway in the pathogenesis of gastric cancer, drawing upon the most recent and critical studies that shed light on MAPK pathway alterations as a gateway to the disease. It highlights the pathway's involvement in Helicobacter pylori-mediated gastric carcinogenesis and the tumorigenic processes induced by the Epstein-Barr virus, showcasing the substantial influence of miRNAs and lncRNAs in modulating gastric cancer's biological properties through their interaction with the MAPK pathway. Furthermore, the review extends into the therapeutic arena, discussing the promising impacts of herbal medicines, MAPK pathway inhibitors, and immunosuppressants on mitigating gastric cancer's progression. Through an exhaustive examination of the MAPK pathway's multifaceted role in gastric cancer, from molecular crosstalks to therapeutic prospects, this review aspires to contribute to the ongoing efforts in understanding and combating this global health challenge, paving the way for novel therapeutic interventions and improved patient outcomes.
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Affiliation(s)
- Weiwei Yuan
- Department of Thyroid Surgery, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China
| | - Yin Shi
- Department of Internal Medicine, Yiwu Maternity and Children Hospital, Yiwu, Zhejiang, China
| | - Shiping Dai
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Mao Deng
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Kai Zhu
- Department of General Surgery, Wuwei City People's Hospital, No.256, West Street, Wuwei, 238300, China
| | - Yuanmin Xu
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zhangming Chen
- Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Zhou Xu
- Department of Thyroid Surgery, Baoshan Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China.
| | - Tianlong Zhang
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
| | - Song Liang
- Department of General Surgery, The Lu'an Affiliated Hospital of Anhui Medical University, Lu'an People's Hospital, Lu'an, 237000, China.
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13
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Yan BB, Cheng LN, Yang H, Li XL, Wang XQ. Comprehensive analysis of risk factors associated with submucosal invasion in patients with early-stage gastric cancer. World J Gastroenterol 2024; 30:5007-5017. [PMID: 39713166 PMCID: PMC11612861 DOI: 10.3748/wjg.v30.i47.5007] [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: 09/05/2024] [Revised: 10/25/2024] [Accepted: 10/31/2024] [Indexed: 11/26/2024] Open
Abstract
BACKGROUND Submucosal invasion in early-stage gastric cancer (GC) is a critical determinant of prognosis and treatment strategy, significantly influencing the risk of lymph node metastasis and recurrence. Identifying risk factors associated with submucosal invasion is essential for optimizing patient management and improving outcomes. AIM To comprehensively analyze clinical, imaging, and endoscopic characteristics to identify predictors of submucosal invasion in patients with early-stage differentiated GC. METHODS A retrospective study was conducted at our institution from January 2019 to January 2023, including 268 patients diagnosed with early-stage differentiated GC who underwent surgical resection or endoscopic submucosal dissection. Data were collected on demographic, clinical, imaging, and endoscopic characteristics, with endoscopic images reviewed independently by two gastroenterologists. Statistical analysis included univariate and multivariate logistic regression to identify significant predictors of submucosal invasion, and receiver operating characteristic (ROC) curve analysis to evaluate the predictive value of continuous variables. RESULTS A total of 268 patients were included, with 178 males and 90 females, and a mean age of 61.5 ± 9.8 years. Univariate analysis showed that male gender, history of alcohol consumption, smoking, and computed tomography-detected gastric wall thickening were more prevalent in patients with submucosal invasion. Significant endoscopic predictors included tumor location in the upper two-thirds of the stomach, depressed morphology, marginal elevation, and high color differences on white-light endoscopy (WLE) and linked color imaging (LCI). Multivariate analysis identified upper stomach location [odds ratio (OR): 5.268], depressed type (OR: 5.841), marginal elevation (OR: 4.132), and LCI color difference ≥ 18.1 (OR: 4.479) as significant predictors. ROC analysis showed moderate predictive value for lesion diameter, WLE, and LCI color differences (area under the curve: 0.630, 0.799, and 0.760, respectively). CONCLUSION Depressed-type lesions, marginal elevation, location in the upper two-thirds of the stomach, and significant color differences on LCI are high-risk indicators for submucosal invasion. These findings suggest that such lesions warrant more aggressive intervention to prevent disease progression and improve patient outcomes.
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Affiliation(s)
- Bin-Bin Yan
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China
| | - Li-Na Cheng
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China
| | - Hui Yang
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China
| | - Xiu-Ling Li
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China
| | - Xiu-Qi Wang
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450000, Henan Province, China
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14
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Bu C, Wang Z, Lv X, Zhao Y. A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection. Epigenetics 2024; 19:2374988. [PMID: 39003776 PMCID: PMC11249030 DOI: 10.1080/15592294.2024.2374988] [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: 01/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2-ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.
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Affiliation(s)
- Chunxiao Bu
- Department of Magnetic Resonance Imaging,The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhilong Wang
- Henan Academy of Medical Sciences, Zhengzhou, Henan, China
| | - Xianping Lv
- Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yanteng Zhao
- Department of Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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15
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Chen Z, Zhang X, Li Z, Zhang H, Wang Z. lncRNA LINC02323 predicts adverse neoadjuvant chemotherapy outcomes of gastric cancer patients and regulates cell sensitivity to 5-fluorouracil by negatively modulating miR-139-3p. Ann Med 2024; 56:2424513. [PMID: 39506605 PMCID: PMC11544739 DOI: 10.1080/07853890.2024.2424513] [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: 03/19/2024] [Revised: 08/13/2024] [Accepted: 10/18/2024] [Indexed: 11/08/2024] Open
Abstract
BACKGROUND/OBJECTIVE Drug resistance is a challenging problem in the clinical chemotherapy of gastric cancer. Identification of predictive biomarkers for chemotherapy outcomes could improve therapeutic efficacy and patient prognosis. This study aimed to assess the significance of long non-coding RNA (lncRNA) LINC02323 in gastric cancer progression and neoadjuvant chemotherapy and to explore its potential regulatory mechanism. MATERIALS AND METHODS This study enrolled 117 patients with gastric cancer who received neoadjuvant chemotherapy combined with surgical treatment and 35 patients with benign gastroscopic results. The expression of LINC02323 in gastric mucosal tissues of study subjects was analyzed by PCR, and its association with chemotherapy efficacy and cancer development was evaluated. Gastric cancer cells were treated with 5-FU, and the effect of LINC02323 on cell growth and motility under 5-FU treatments was evaluated using CCK8 and transwell assays. RESULTS LINC02323 was upregulated in gastric cancer patients, which was related to advanced T stage, occurrence of lymph node metastasis, and less pathological response to chemotherapy. LINC02323 serves as a prognostic biomarker for predicting poor overall survival of gastric cancer patients receiving neoadjuvant chemotherapy. Silencing LINC02323 suppressed the proliferation and motility of gastric cancer cells treated with 5-FU and induced cell apoptosis, indicating the enhanced sensitivity of gastric cancer cells to 5-FU. miR-139-3p was negatively regulated by LINC02323 and could reverse the function of LINC02323 in 5-FU-treated gastric cancer cells. CONCLUSION Upregulated LINC02323 expression in gastric cancer is associated with malignant progression, adverse prognosis, and chemotherapy resistance. Silencing LINC02323 could enhance the sensitivity of gastric cancer cells to 5-FU by negatively modulating miR-139-3p expression.
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Affiliation(s)
- Zexu Chen
- Department of General Surgery, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Xiaodong Zhang
- Department of Gastroenterology, Nanjing LuHe People’s Hospital, Nanjing, Jiangsu, China
| | - Zhentao Li
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to XuZhou Medical University, Xuzhou, Jiangsu, China
| | - Haihan Zhang
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to XuZhou Medical University, Xuzhou, Jiangsu, China
| | - Zhuangmei Wang
- Department of Gastroenterology, Xuzhou Municipal Hospital Affiliated to XuZhou Medical University, Xuzhou, Jiangsu, China
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16
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Hayashi T, Sano K, Okada M, Muto M, Konishi I. Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. Curr Oncol 2024; 31:6723-6734. [PMID: 39590127 PMCID: PMC11592444 DOI: 10.3390/curroncol31110496] [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: 09/03/2024] [Revised: 10/24/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%). H. pylori infection causes GC in >98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.
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Affiliation(s)
- Takuma Hayashi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
| | - Kenji Sano
- Pathological Division, Shinshu University Hospital, Matsumoto 390-0877, Nagano, Japan
| | - Mako Okada
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
| | - Manabu Muto
- Medical Oncology, Kyoto University Hospital, Kyoto 612-8555, Kyoto, Japan
| | - Ikuo Konishi
- Cancer Medicine, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto 612-8555, Kyoto, Japan
- Department of Medical Oncology, Kyoto University School of Medicine, Kyoto 606-8507, Kyoto, Japan
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17
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Chen Y, Ma Y, Wu H, Wei X, Xu Z, Wang Q. Examining the relationship between preoperative nutritional and symptom assessment and postoperative atrial fibrillation in esophageal squamous cell carcinoma patients: a retrospective cohort study. BMC Surg 2024; 24:298. [PMID: 39385162 PMCID: PMC11463059 DOI: 10.1186/s12893-024-02609-7] [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: 02/16/2024] [Accepted: 10/01/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVE The study aimed to examine the relationship between preoperative nutritional status, symptom burden, and the occurrence of postoperative atrial fibrillation in Esophageal Squamous Cell Carcinoma patients. METHODS The study, conducted in the Department of Thoracic Surgery at the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, applied the NRS 2002, SGA and MSAS scoring systems as measures of nutritional status and symptom occurrence in patients diagnosed with ESCC. Univariate and multivariate logistic regression analysis were performed to evaluate the association between nutritional scores, symptom scores, and postoperative complications. RESULTS The research found a significant correlation between high MSAS scores and postoperative atrial fibrillation. Patients with high symptom burden also tended to have nutritional risk or malnutrition according to the NRS2002 and SGA scores. CONCLUSION There is a need for healthcare providers to pay attention to ESCC patients' physical and psychological symptoms. Close monitoring of nutritional status and timely nutritional interventions should be integrated into these patients' care plans as they have been found to be related to postoperative complications such as atrial fibrillation.
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Affiliation(s)
- Yunyun Chen
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Yan Ma
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Haiyan Wu
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Xinqi Wei
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China
| | - Zhiyun Xu
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
| | - Qingmei Wang
- Department of Thoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
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18
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Tong X, Du J, Jiang Q, Wu Q, Zhao S, Chen S. Lenvatinib acts on platelet‑derived growth factor receptor β to suppress the malignant behaviors of gastric cancer cells. Oncol Lett 2024; 28:483. [PMID: 39170883 PMCID: PMC11338234 DOI: 10.3892/ol.2024.14616] [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: 03/29/2024] [Accepted: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Given the limited treatment options and high mortality rates associated with gastric cancer, there is a need to explore novel therapeutic options. The present study aimed to investigate the efficacy of lenvatinib, a multi-target tyrosine kinase inhibitor, in mitigating the progress of gastric cancer in vitro. Comprehensive analyses were conducted to assess the impact of lenvatinib on gastric cancer cells, focusing on the inhibition of viability, suppression of proliferation, induction of apoptosis and reduction of metastatic potential. The effects of lenvatinib on these activities were determined using 5-ethynyl-2'-deoxyuridine staining, colony formation assay, flow cytometry, western blotting, scratch assay and Transwell assay. In addition, bioinformatics analyses were employed to identify key regulatory targets of lenvatinib, with particular attention given to platelet-derived growth factor receptor β (PDGFRB). In addition, the effects of PDGFRB overexpression on the regulation of lenvatinib were explored. Lenvatinib demonstrated significant inhibitory effects on the viability, proliferation and metastatic capabilities of MKN45 and HGC27 gastric cancer cell lines. Bioinformatics analyses identified PDGFRB as a crucial target of lenvatinib, with its downregulation showing promise in enhancing overall survival rates of patients with gastric cancer. By contrast, PDGFRB overexpression reversed the effects of lenvatinib on cells. The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements.
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Affiliation(s)
- Xiaoyi Tong
- Graduate School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Jun Du
- Department of Nursing, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Qiaoling Jiang
- Department of Clinical Laboratory, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Qiaoli Wu
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Shuxia Zhao
- Department of Pharmacy, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
| | - Shuhang Chen
- Department of Gastroenterology, Lanxi People's Hospital, Jinhua, Zhejiang 321100, P.R. China
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Zhao H, Shi XY, Lv LL, Lai YZ, Bao XX, Hu JW. Clinical characteristics of patients with early gastric prematurity cancer and analysis of complications by endoscopic resection. World J Gastrointest Oncol 2024; 16:3898-3904. [PMID: 39350991 PMCID: PMC11438787 DOI: 10.4251/wjgo.v16.i9.3898] [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: 07/24/2024] [Revised: 08/07/2024] [Accepted: 08/09/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Gastric cancer, a prevalent malignancy, poses a severe threat to the health of residents in China. Timely intervention in early stages can extend patients' survival. AIM To analyze clinical characteristics of patients with early gastric cancer and efficacy and risk of complications associated with endoscopic resection. METHODS This study included 175 patients with early gastric cancer treated at our hospital, with no restrictions on sex or age. General data, pathological information, and endoscopic biopsy results were obtained. The clinical characteristics of early gastric cancer were analyzed, and endoscopic resection was performed. Postoperative efficacy and incidence of complications were monitored. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0 software. RESULTS A total of 175 patients with early gastric cancer were included, with 75.43% (n = 132) males and 24.57% (n = 43) females. 38.29% (n = 67) and 35.43% (n = 62) of patients had a history of smoking and alcohol consumption, respectively. Comorbidities included diabetes (8.57%, n = 15), coronary heart disease (10.29%, n = 18), and hypertension (43.43%, n = 76), which was highly prevalent. A history of abdominal surgery and family history of digestive system cancer accounted for 21.14% and 17.14%, respectively. The most common lesion location was the antral part of the stomach (52.00%, n = 91), followed by the gastric angle, body, and fundus. The pathological types were predominantly high-grade intraepithelial neoplasia (28.00%, n = 49) and well-differentiated adenocarcinoma (26.86%, n = 47), followed by moderately differentiated adenocarcinoma, high-moderately differentiated adenocarcinoma, and moderate-lowly differentiated adenocarcinoma. 89.14% of the patients had intestinal metaplasia and 85.14% had atrophy. After endoscopic resection, re-examination revealed that 13 patients had cancer cells at the tissue margin, with a positive margin rate of 7.43%. Postoperative complications included no cases of gastrointestinal obstruction, but incisional infection (2.86%, n = 5), gastric perforation (1.14%, n = 2), and gastric bleeding (4%, n = 7) were present, with an overall incidence of 8.00%. CONCLUSION Analysis of the clinical characteristics indicated that early gastric cancer is more prevalent in males with a history of hypertension, with lesions most commonly occurring in the antral region of the stomach. The pathological types are often high-grade intraepithelial neoplasia and well-differentiated adenocarcinoma, with over 85% of patients having comorbid intestinal metaplasia and atrophy. Despite endoscopic resection, a positive margin rate persisted, indicating a probability of residual cancer at the margins. Postoperative complications, such as gastrointestinal obstruction, incisional infection, gastric perforation, and gastric bleeding can occur and require timely symptomatic treatment.
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Affiliation(s)
- Hong Zhao
- Department of Gastroenterology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
| | - Xiang-Yu Shi
- Department of Gastroenterology, Yiwu Tianxiang Medical East Hospital, Yiwu 322100, Zhejiang Province, China
| | - Li-Li Lv
- Department of Gastroenterology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
| | - Yan-Zong Lai
- Department of Gastroenterology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
| | - Xiao-Xiao Bao
- Department of Pathology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
| | - Jian-Wen Hu
- Department of Gastroenterology, Dongyang People’s Hospital, Dongyang 322100, Zhejiang Province, China
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Jia J, Zhao H, Li F, Zheng Q, Wang G, Li D, Liu Y. Research on drug treatment and the novel signaling pathway of chronic atrophic gastritis. Biomed Pharmacother 2024; 176:116912. [PMID: 38850667 DOI: 10.1016/j.biopha.2024.116912] [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: 04/16/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/10/2024] Open
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ β-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.
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Affiliation(s)
- Jinhao Jia
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Huijie Zhao
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Fangfei Li
- Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Special Administrative Region of China
| | - Qiusheng Zheng
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China
| | - Guoli Wang
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China
| | - Defang Li
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, Xinjiang 832003, PR China.
| | - Ying Liu
- Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Traditional Chinese Medicine & Binzhou Hospital of Traditional Chinese Medicine, Binzhou Medical University, Yantai, Shandong 264003, PR China.
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Zhu Y, Ji M, Yuan L, Yuan J, Shen L. A risk prediction model for delayed bleeding after ESD for gastric precancerous lesions. Surg Endosc 2024; 38:3967-3975. [PMID: 38844732 DOI: 10.1007/s00464-024-10923-7] [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: 01/22/2024] [Accepted: 05/03/2024] [Indexed: 07/03/2024]
Abstract
OBJECTIVE To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model. METHODS This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model. RESULTS Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability. CONCLUSION In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients.
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Affiliation(s)
- Yiying Zhu
- Department of Gastroenterology, Wuhan University Renmin Hospital, Wuhan, 430060, Hubei, China
| | - Mengyao Ji
- Department of Gastroenterology, Wuhan University Renmin Hospital, Wuhan, 430060, Hubei, China
- Key Laboratory of Hubei Province for Digestive System Disease, Wuhan University Renmin Hospital, Wuhan, Hubei, China
| | - Lei Yuan
- Department of Information Center, Wuhan University Renmin Hospital, Wuhan, Hubei, China
- School of Automation, Nanjing University of Information Science and Technology, Nanjing, China
- Key Laboratory of Hubei Province for Digestive System Disease, Wuhan University Renmin Hospital, Wuhan, Hubei, China
| | - Jingping Yuan
- Department of Pathology, Wuhan University Renmin Hospital, Wuhan, Hubei, China
| | - Lei Shen
- Department of Gastroenterology, Wuhan University Renmin Hospital, Wuhan, 430060, Hubei, China.
- Key Laboratory of Hubei Province for Digestive System Disease, Wuhan University Renmin Hospital, Wuhan, Hubei, China.
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Yu C, Zhou G, Shi Z, Yu L, Zhou X. TREM1 facilitates the development of gastric cancer through regulating neutrophil extracellular traps-mediated macrophage polarization. Dig Liver Dis 2024; 56:1237-1247. [PMID: 38151453 DOI: 10.1016/j.dld.2023.12.002] [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: 05/19/2023] [Revised: 12/04/2023] [Accepted: 12/07/2023] [Indexed: 12/29/2023]
Abstract
Triggering receptor expressed on myeloid cell 1 (TREM1) elevation is associated with the unfavorable prognosis of gastric cancer (GC) patients. This work uncovered the effects and mechanism of TREM1 in GC. IHC staining examined TREM1 expression in GC tissues. TREM1-knockout and TREM1 knock-in mice were generated prior to the construction of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GC mice model. H&E staining detected the pathological alternations of gastric tissues. IHC staining tested Ki67 expression. Wright-Giemsa staining performed neutrophil counting and flow cytometry analysis measured neutrophil infiltration. ELISA analyzed serum and tissue myeloperoxidase (MPO) levels and serum MPO-DNA levels. Immunofluorescence, Western blotting and related kits detected NETs formation. Immunofluorescence and IHC staining evaluated macrophage polarization. In MNNG-treated GES-1 cells and phorbal myristate acetate (PMA)-treated neutrophils, TREM1 expression was also examined. CCK-8 method and Western blotting assayed cell proliferation. Western blotting and immunofluorescence detected NETs formation. Flow cytometry analysis detected the changes of macrophage typing. TREM1 was overexpressed in tumor tissues, MNNG-treated GES-1 cells and PMA-treated neutrophils. TREM1 deficiency hindered tumor growth, reduced neutrophil infiltration, NETs formation and stimulated M1 macrophage polarization in MNNG-induced GC models. Neutrophil extracellular traps (NETs) degrader DNase-1 countervailed the impacts of TREM1 on MNNG-induced GC models in vivo. Collectively, TREM1 knockdown obstructed NETs-mediated M2 macrophage polarization to hamper GC progression.
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Affiliation(s)
- Cheng Yu
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Guoqiang Zhou
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Zhiliang Shi
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Liang Yu
- Department of General Surgery, Affiliated Changshu Hospital of Nantong University, Changshu, 215500, China
| | - Xiaojun Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
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Shi Z, Guo X, Hu X, Li R, Li X, Lu J, Jin M, Jiang X. DNA methylation profiling identifies epigenetic signatures of early gastric cancer. Virchows Arch 2024; 484:687-695. [PMID: 38507065 DOI: 10.1007/s00428-024-03765-0] [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: 08/20/2023] [Revised: 01/23/2024] [Accepted: 02/08/2024] [Indexed: 03/22/2024]
Abstract
Research on the DNA methylation status of gastric cancer (GC) has primarily focused on identifying invasive GC to develop biomarkers for diagnostic. However, DNA methylation in noninvasive GC remains unclear. We conducted a comprehensive DNA methylation profiling study of differentiated-type intramucosal GCs (IMCs). Illumina 850K microarrays were utilized to assess the DNA methylation profiles of formalin-fixed paraffin-embedded tissues from eight patients who were Epstein-Barr virus-negative and DNA mismatch repair proficient, including IMCs and paired adjacent nontumor mucosa. Gene expression profiling microarray data from the GEO database were analyzed via bioinformatics to identify candidate methylation genes. The final validation was conducted using quantitative real-time PCR, the TCGA methylation database, and single-sample gene set enrichment analysis (GSEA). Genome-wide DNA methylation profiling revealed a global decrease in methylation in IMCs compared with nontumor tissues. Differential methylation analysis between IMCs and nontumor tissues identified 449 differentially methylated probes, with a majority of sites showing hypomethylation in IMCs compared with nontumor tissues (66.1% vs 33.9%). Integrating two RNA-seq microarray datasets, we found one hypomethylation-upregulated gene: eEF1A2, overlapped with our DNA methylation data. The mRNA expression of eEF1A2 was higher in twenty-four IMC tissues than in their paired adjacent nontumor tissues. GSEA indicated that the functions of eEF1A2 were associated with the development of IMCs. Furthermore, TCGA data indicated that eEF1A2 is hypomethylated in advanced GC. Our study illustrates the implications of DNA methylation alterations in IMCs and suggests that aberrant hypomethylation and high mRNA expression of eEF1A2 might play a role in IMCs development.
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Affiliation(s)
- Zhongyue Shi
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xinmeng Guo
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xiumei Hu
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Ruiqi Li
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xue Li
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jun Lu
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Mulan Jin
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
| | - Xingran Jiang
- Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
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24
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Ma Z, Zhou Z, Duan W, Yao G, Sheng S, Zong S, Zhang X, Li C, Liu Y, Ou F, Dahar MR, Huang Y, Yu L. DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy. Cancer Immunol Immunother 2024; 73:82. [PMID: 38554200 PMCID: PMC10981630 DOI: 10.1007/s00262-024-03673-x] [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: 02/20/2024] [Accepted: 03/08/2024] [Indexed: 04/01/2024]
Abstract
BACKGROUND Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma. The T cell engager targeting CLDN18.2 represents a compelling strategy for enhancing anti-cancer efficacy. METHODS Based on the in-house screened anti-CLDN18.2 VHH, we have developed a novel tri-specific T cell engager targeting CLDN18.2 for gastric and pancreatic cancer immunotherapy. This tri-specific antibody was designed with binding to CLDN18.2, human serum albumin (HSA) and CD3 on T cells. RESULTS The DR30318 demonstrated binding affinity to CLDN18.2, HSA and CD3, and exhibited T cell-dependent cellular cytotoxicity (TDCC) activity in vitro. Pharmacokinetic analysis revealed a half-life of 22.2-28.6 h in rodents and 41.8 h in cynomolgus monkeys, respectively. The administration of DR30318 resulted in a slight increase in the levels of IL-6 and C-reactive protein (CRP) in cynomolgus monkeys. Furthermore, after incubation with human PBMCs and CLDN18.2 expressing cells, DR30318 induced TDCC activity and the production of interleukin-6 (IL-6) and interferon-gamma (IFN-γ). Notably, DR30318 demonstrated significant tumor suppression effects on gastric cancer xenograft models NUGC4/hCLDN18.2 and pancreatic cancer xenograft model BxPC3/hCLDN18.2 without affecting the body weight of mice.
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Affiliation(s)
- Zhe Ma
- Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Zhenxing Zhou
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Wenwen Duan
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Gaofeng Yao
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Shimei Sheng
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Sidou Zong
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Xin Zhang
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Changkui Li
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Yuanyuan Liu
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China
| | - Fengting Ou
- Jinhua Institute of Zhejiang University, Jinhua, 321036, China
| | - Maha Raja Dahar
- Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
| | - Yanshan Huang
- Department of Innovative Drug Discovery and Development, Zhejiang Doer Biologics Co., Ltd., Hangzhou, 310058, Zhejiang Province, China.
| | - Lushan Yu
- Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China.
- National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, 310058, China.
- Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
- Jinhua Institute of Zhejiang University, Jinhua, 321036, China.
- Department of Pharmacy, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, China.
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Tan Y, Feng LJ, Huang YH, Xue JW, Feng ZB, Long LL. Development and validation of a Radiopathomics model based on CT scans and whole slide images for discriminating between Stage I-II and Stage III gastric cancer. BMC Cancer 2024; 24:368. [PMID: 38519974 PMCID: PMC10960497 DOI: 10.1186/s12885-024-12021-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/18/2024] [Indexed: 03/25/2024] Open
Abstract
OBJECTIVE This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III). METHODS This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA). RESULTS A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility. CONCLUSION The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.
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Affiliation(s)
- Yang Tan
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Li-Juan Feng
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Ying-He Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Jia-Wen Xue
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Zhen-Bo Feng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
| | - Li-Ling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Gaungxi Medical University, Ministry of Education, Nanning, Guangxi, China.
- Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, China.
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Zhang Y, Shi F, Fan Y, Liu G, Xia C, Wang H. Comparison of prognostic outcomes between endoscopic submucosal dissection and surgical treatment for early gastric cancer: a retrospective cohort study. BMC Gastroenterol 2024; 24:98. [PMID: 38438982 PMCID: PMC10913608 DOI: 10.1186/s12876-024-03186-y] [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: 07/04/2023] [Accepted: 02/22/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND AND AIM The optimal management strategy for early gastric cancer (EGC) a topic of contention. This study aims to compare the prognostic outcomes of endoscopic submucosal dissection (ESD) and surgical treatment in patients diagnosed with EGC. METHODS In thisretrospective cohort study, we analyzed data from539 patients diagnosed with EGC between January 2012 and December 2020 from two centers. We compared Clinicopathological features, procedure-related complications, recurrence rate, overall survival, and disease specific survival between the 262 patients who underwent ESD and the 277 patients who underwent surgical treatment. ESD procedures were conducted using a dual knife by experienced endoscopists, while surgical treatments included laparoscopic or open gastrectomy. Regular ollow-up examinations were conducted post-treatment. RESULTS The two groups exhibited comparable baseline characteristics. Multivariable Cox regression analysis identified vascular invasion as a risk factor for worse recurrence-free survival (RFS), and overall survival (OS) in patients with early gastric cancer. The ESD group experienced fewer overall postoperative complications compared to the surgical treatment group. Kaplan-Meier curves demonstrated no significant differences in recurrence rate or overall survival between the two groups. CONCLUSIONS Both ESD and surgical treatment emerged as safe and effective approaches for managing EGC. The choice of treatment should be tailored to individual patient factors. ESD can be considered an alternative treatment option for selected patients who are not suitable candidates for surgery. Further studies are warranted to determine the long-term outcomes of ESD and surgical treatment for EGC.
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Affiliation(s)
- Yifan Zhang
- Department of Gastrointestinal Surgery, Affiliated Kunshan Hospital to Jiangsu University, 215300, Suzhou, Jiangsu, China
| | - Fangzhen Shi
- Department of Gastroenterology, Kunshan Sixth People's Hospital, 215321, Suzhou, Jiangsu, China
| | - Yuxiang Fan
- Department of General Surgery, Kunshan Sixth People's Hospital, 215321, Suzhou, Jiangsu, China
| | - Gang Liu
- Department of Emergency Surgery, Affiliated Kunshan Hospital to Jiangsu University, 215300, Suzhou, Jiangsu, China
| | - Chengkai Xia
- Department of Emergency Surgery, Affiliated Kunshan Hospital to Jiangsu University, 215300, Suzhou, Jiangsu, China
| | - Haodong Wang
- Department of Emergency Surgery, Affiliated Kunshan Hospital to Jiangsu University, 215300, Suzhou, Jiangsu, China.
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Morgos DT, Stefani C, Miricescu D, Greabu M, Stanciu S, Nica S, Stanescu-Spinu II, Balan DG, Balcangiu-Stroescu AE, Coculescu EC, Georgescu DE, Nica RI. Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. Int J Mol Sci 2024; 25:1848. [PMID: 38339127 PMCID: PMC10856016 DOI: 10.3390/ijms25031848] [Citation(s) in RCA: 55] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/26/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.
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Affiliation(s)
- Diana-Theodora Morgos
- Discipline of Anatomy, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Constantin Stefani
- Department I of Family Medicine and Clinical Base, “Dr. Carol Davila” Central Military Emergency University Hospital, 010825 Bucharest, Romania
| | - Daniela Miricescu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Maria Greabu
- Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Silviu Stanciu
- Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania;
| | - Silvia Nica
- Emergency Discipline, University Hospital of Bucharest, 050098 Bucharest, Romania;
| | - Iulia-Ioana Stanescu-Spinu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Daniela Gabriela Balan
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Andra-Elena Balcangiu-Stroescu
- Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (I.-I.S.-S.); (D.G.B.); (A.-E.B.-S.)
| | - Elena-Claudia Coculescu
- Discipline of Oral Pathology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Dragos-Eugen Georgescu
- Department of General Surgery, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 50474 Bucharest, Romania;
- Department of General Surgery, “Dr. Ion Cantacuzino” Clinical Hospital, 020475 Bucharest, Romania
| | - Remus Iulian Nica
- Central Military Emergency University Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania;
- Discipline of General Surgery, Faculty of Midwifery and Nursing, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
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Tan Y, Feng LJ, Huang YH, Xue JW, Long LL, Feng ZB. A comprehensive radiopathological nomogram for the prediction of pathological staging in gastric cancer using CT-derived and WSI-based features. Transl Oncol 2024; 40:101864. [PMID: 38141376 PMCID: PMC10788295 DOI: 10.1016/j.tranon.2023.101864] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 12/08/2023] [Accepted: 12/12/2023] [Indexed: 12/25/2023] Open
Abstract
OBJECTIVE This study aims to develop and validate an innovative radiopathomics model that combines radiomics and pathomics features to effectively differentiate between stages I-II and stage III gastric cancer (pathological staging). METHODS Our study included 200 patients with well-defined stages of gastric cancer divided into a training cohort (n = 140) and a test cohort (n = 60). Radiomics features were extracted from contrast-enhanced CT images using PyRadiomics, while pathomics features were obtained from whole slide images of pathological specimens through a fine-tuned deep learning model (ResNet-18). After rigorous feature dimensionality reduction and selection, we constructed radiomics models (SVM_rad, LR_rad, and MLP_rad) and pathomics models (SVM_path, LR_path, and MLP_path) utilizing support vector machine (SVM), logistic regression (LR), and multilayer perceptron (MLP) algorithms. The optimal radiomics and pathomics models were chosen based on comprehensive evaluation criteria such as ROC curves, Hosmer‒Lemeshow tests, and calibration curve tests. Feature patterns extracted from the best-performing radiomics model (MLP_rad) and pathomics model (SVM_rad) were integrated to create a powerful radiopathomics nomogram. RESULTS From a pool of 1834 radiomics features extracted from CT images, 14 were selected to construct radiomics models. Among these, the MLP_rad model exhibited the most robust predictive performance (AUC, training cohort: 0.843; test cohort: 0.797). Likewise, 10 pathomics features were chosen from 512 extracted from whole slide images to build pathomics models, with the SVM_path model demonstrating the highest predictive efficiency (AUC, training cohort: 0.937; test cohort: 0.792). The combined radiopathomics nomogram model exhibited optimal discriminative ability (AUC, training cohort: 0.951; test cohort: 0.837), as confirmed by decision curve analysis (DCA), which indicated superior clinical effectiveness. CONCLUSION This study presents a cutting-edge radiopathomics nomogram model designed to predict pathological staging in gastric cancer, distinguishing between stages I-II and stage III. Our research leverages preoperative CT images and histopathological slides to forecast gastric cancer staging accurately, potentially facilitating the estimation of staging before radical gastric cancer surgery in the future.
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Affiliation(s)
- Yang Tan
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Li-Juan Feng
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Ying-He Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, PR China
| | - Jia-Wen Xue
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China
| | - Li-Ling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Gaungxi Medical University, Ministry of Education, Nanning, Guangxi, PR China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, PR China.
| | - Zhen-Bo Feng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China.
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Zha L, Guo X, Liang X, Chen Y, Gan D, Li W, Wang Z, Zhang H. Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma. Genes Dis 2023; 10:2614-2621. [PMID: 37554183 PMCID: PMC10404868 DOI: 10.1016/j.gendis.2022.10.027] [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: 05/09/2022] [Revised: 08/09/2022] [Accepted: 10/23/2022] [Indexed: 12/13/2022] Open
Abstract
Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage disease do not have lymph node metastasis, which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study, the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the Helicobacter pylori (HP) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the HP infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism, we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2), which was not only clustered in the gene set of epithelial cells signaling in the HP infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients. HP infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.
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Affiliation(s)
- Lang Zha
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Xiong Guo
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Xiaolong Liang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Yuedong Chen
- Department of Gastrointestinal Surgery, The Tongliang Hospital of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Deyong Gan
- Department of Gastrointestinal Surgery, The Tongliang Hospital of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Wenwen Li
- Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
| | - Ziwei Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Hongyu Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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Yin JJ, Hu X, Hu S, Sheng GH. Efficacy of multi-slice spiral computed tomography in evaluating gastric cancer recurrence after endoscopic submucosal dissection. World J Gastrointest Oncol 2023; 15:1636-1643. [PMID: 37746651 PMCID: PMC10514731 DOI: 10.4251/wjgo.v15.i9.1636] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 07/25/2023] [Accepted: 08/08/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Recurrence is the major challenge facing endoscopic submucosal dissection (ESD)-based treatment therapies for early gastric cancer (EGC). Urgent development of simple and easy surveillance approaches will enhance clinical treatment of the disease. AIM To explore the role of computed tomography (CT) recurrence in evaluating EGC after ESD treatment. METHODS We retrospectively recruited patients from our endoscopy department, between January 2002 and December 2015, and analyzed their basic characteristics, including symptoms, CT results, and results of endoscopy with biopsy, among others. RESULTS Among a total of 2150 patients EGC patients surveyed, 1362 met our inclusion and exclusion criteria and were therefore enrolled in our study. The cohort's sensitivity of CT for recurrent GC and specificity were 44.22% and 43.86%, respectively, with negative and positive predictive values of 40.15% (275/685) and 48.01% (325/677), respectively. The area under the curve of arterial and venous CT values for recurrent EGC were 0.545, and 0.604, respectively. Receiver operating characteristic curve revealed no statistically significant differences between arterial and venous CT values for recurrent EGC. CONCLUSION Enhanced CT has superior diagnostic efficacy, but less accuracy, compared to gold standard techniques in patients with recurrent EGC.
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Affiliation(s)
- Jian-Jun Yin
- Department of Radiology, Huangshi Maternity and Children's health Hospital, Affiliated Maternity and Children's Health Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China
| | - Xiao Hu
- Department of Geriatrics, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China
| | - Sen Hu
- Department of Radiology, Huangshi Maternity and Children's health Hospital, Affiliated Maternity and Children's Health Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China
| | - Guo-Hong Sheng
- Department of Radiology, Huangshi Maternity and Children's health Hospital, Affiliated Maternity and Children's Health Hospital of Hubei Polytechnic University, Huangshi 435000, Hubei Province, China
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Popovic D, Glisic T, Milosavljevic T, Panic N, Marjanovic-Haljilji M, Mijac D, Stojkovic Lalosevic M, Nestorov J, Dragasevic S, Savic P, Filipovic B. The Importance of Artificial Intelligence in Upper Gastrointestinal Endoscopy. Diagnostics (Basel) 2023; 13:2862. [PMID: 37761229 PMCID: PMC10528171 DOI: 10.3390/diagnostics13182862] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 08/28/2023] [Accepted: 09/01/2023] [Indexed: 09/16/2023] Open
Abstract
Recently, there has been a growing interest in the application of artificial intelligence (AI) in medicine, especially in specialties where visualization methods are applied. AI is defined as a computer's ability to achieve human cognitive performance, which is accomplished through enabling computer "learning". This can be conducted in two ways, as machine learning and deep learning. Deep learning is a complex learning system involving the application of artificial neural networks, whose algorithms imitate the human form of learning. Upper gastrointestinal endoscopy allows examination of the esophagus, stomach and duodenum. In addition to the quality of endoscopic equipment and patient preparation, the performance of upper endoscopy depends on the experience and knowledge of the endoscopist. The application of artificial intelligence in endoscopy refers to computer-aided detection and the more complex computer-aided diagnosis. The application of AI in upper endoscopy is aimed at improving the detection of premalignant and malignant lesions, with special attention on the early detection of dysplasia in Barrett's esophagus, the early detection of esophageal and stomach cancer and the detection of H. pylori infection. Artificial intelligence reduces the workload of endoscopists, is not influenced by human factors and increases the diagnostic accuracy and quality of endoscopic methods.
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Affiliation(s)
- Dusan Popovic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Department of Gastroenterology, Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, 11000 Belgrade, Serbia; (N.P.); (M.M.-H.)
| | - Tijana Glisic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | | | - Natasa Panic
- Department of Gastroenterology, Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, 11000 Belgrade, Serbia; (N.P.); (M.M.-H.)
| | - Marija Marjanovic-Haljilji
- Department of Gastroenterology, Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, 11000 Belgrade, Serbia; (N.P.); (M.M.-H.)
| | - Dragana Mijac
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Milica Stojkovic Lalosevic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Jelena Nestorov
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Sanja Dragasevic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Gastroenterohepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Predrag Savic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Clinic for Surgery, Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, 11000 Belgrade, Serbia
| | - Branka Filipovic
- Faculty of Medicine Belgrade, University of Belgrade, 11000 Belgrade, Serbia; (T.G.); (D.M.); (M.S.L.); (J.N.); (S.D.); (P.S.); (B.F.)
- Department of Gastroenterology, Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, 11000 Belgrade, Serbia; (N.P.); (M.M.-H.)
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Taghipour Zahir S, Razavi SH, SafiDahaj F, Rahmani K, Sadeghinejad‐Alamabadi S. Prognosis and survival study in patients with gastric adenocarcinoma and its relationship with pRb expression alteration: A retrospective IHC-based study. Health Sci Rep 2023; 6:e1445. [PMID: 37519424 PMCID: PMC10372302 DOI: 10.1002/hsr2.1445] [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: 01/26/2023] [Revised: 03/25/2023] [Accepted: 07/14/2023] [Indexed: 08/01/2023] Open
Abstract
Background and Objective Among cancers, gastric cancer has the fifth highest incidence worldwide and is the third most common mortality factor, which may have been due to inadequate knowledge of its molecular pathogenesis. The retinoblastoma gene (RB1), a tumor suppressor gene, may have a role in gastric cancer. This research aims to assess Rb expression as a prognostic marker to obtain more insight regarding gastric cancer. Methods This retrospective analytical study was done on 61 patients (45 males and 16 females) with gastric adenocarcinoma admitted from 2010 to 2012 in Shahid Sadoughi and Mortaz hospitals, Yazd, Iran. Demographic data, including age, gender, clinical signs and symptoms, and pathology reports, were retrieved from patients' hospital folders. Then, the altered Retinoblastoma gene expression was evaluated by immunohistochemistry studies. Acquired data were analyzed by SPSS software v.16. p < 0.05 was statistically considered meaningful. Results In this study, the ratio of men to women was higher (2.81:1), and the mean age of patients was 62.44 years. About 90.2% of patients died during the study. There was no meaningful relationship between the presence of pRb, the intensity of staining, the percentage of staining with patients' age, gender, tumor grading, and survival rate (p > 0.05). There was only a meaningful relationship between the grade of tumors and survival rate (p = 0.039). Conclusion Altered pRB expression is not common in gastric cancer and does not impact the survival and grading of tumors. Poorly differentiated tumors had an ominous outcome with the lowest survival time.
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Affiliation(s)
| | - Seyyed Hossein Razavi
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
| | - Farzan SafiDahaj
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
| | - Koorosh Rahmani
- Clinical and Surgical PathologyShahid Sadoughi University of Medical SciencesYazdIran
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Jin W, Ou K, Li Y, Liu W, Zhao M. Metabolism-related long non-coding RNA in the stomach cancer associated with 11 AMMLs predictive nomograms for OS in STAD. Front Genet 2023; 14:1127132. [PMID: 36992704 PMCID: PMC10040790 DOI: 10.3389/fgene.2023.1127132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/28/2023] [Indexed: 03/14/2023] Open
Abstract
Background: The metabolic processes involving amino acids are intimately linked to the onset and progression of cancer. Long non-coding RNAs (LncRNAs) perform an indispensable function in the modulation of metabolic processes as well as the advancement of tumors. Non-etheless, research into the role that amino acid metabolism-related LncRNAs (AMMLs) might play in predicting the prognosis of stomach adenocarcinoma (STAD) has not been done. Therefore, This study sought to design a model for AMMLs to predict STAD-related prognosis and elucidate their immune properties and molecular mechanisms.Methods: The STAD RNA-seq data in the TCGA-STAD dataset were randomized into the training and validation groups in a 1:1 ratio, and models were constructed and validated respectively. In the molecular signature database, This study screened for genes involved in amino acid metabolism. AMMLs were obtained by Pearson’s correlation analysis, and predictive risk characteristics were established using least absolute shrinkage and selection operator (LASSO) regression, univariate Cox analysis, and multivariate Cox analysis. Subsequently, the immune and molecular profiles of high- and low-risk patients and the benefit of the drug were examined.Results: Eleven AMMLs (LINC01697, LINC00460, LINC00592, MIR548XHG, LINC02728, RBAKDN, LINCOG, LINC00449, LINC01819, and UBE2R2-AS1) were used to develop a prognostic model. Moreover, high-risk individuals had worse overall survival (OS) than low-risk patients in the validation and comprehensive groups. A high-risk score was associated with cancer metastasis as well as angiogenic pathways and high infiltration of tumor-associated fibroblasts, Treg cells, and M2 macrophages; suppressed immune responses; and a more aggressive phenotype.Conclusion: This study identified a risk signal associated with 11 AMMLs and established predictive nomograms for OS in STAD. These findings will help us personalize treatment for gastric cancer patients.
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Affiliation(s)
- Wenjian Jin
- Department of Hepatopancreatobiliary Surgery, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Kongbo Ou
- Department of Urinary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou First People’s Hospital, Soochow University, Changzhou, China
| | - Yuanyuan Li
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou First People’s Hospital, Soochow University, Changzhou, China
| | - Wensong Liu
- Department of Hepatopancreatobiliary Surgery, Changzhou First People’s Hospital, Third Affiliated Hospital of Soochow University, Changzhou, China
- *Correspondence: Min Zhao, ; Wensong Liu,
| | - Min Zhao
- Department of Gastrointestinal Surgery, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, China
- *Correspondence: Min Zhao, ; Wensong Liu,
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Guo X, Bu X, Yuan L, Ji L. Collagen type V alpha 2 promotes the development of gastric cancer via M2 macrophage polarization. CHINESE J PHYSIOL 2023; 66:93-102. [PMID: 37082997 DOI: 10.4103/cjop.cjop-d-22-00078] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023] Open
Abstract
Gastric cancer is a type of digestive tract cancer with a high morbidity and mortality, which leads to a major health burden worldwide. More research into the functions of the immune system will improve therapy and survival in gastric cancer patients. We attempted to identify potential biomarkers or targets in gastric cancer via bioinformatical analysis approaches. Three gene expression profile datasets (GSE79973, GSE103236, and GSE118916) of gastric tissue samples were obtained from the Gene Expression Omnibus database. There were 65 overlapping differentially expressed genes (DEGs) identified from three microarrays. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway were carried out for the key functions and pathways enriched in the DEGs. Then, ten hub genes were identified by protein-protein interaction network. In addition, we observed that collagen type V alpha 2 (COL5A2) was linked to gastric cancer prognosis as well as M2 macrophage infiltration. Furthermore, COL5A2 enhanced gastric cancer cell proliferation through the PI3K-AKT signaling pathway and polarized M2 macrophage cells. Therefore, in this study, we found that COL5A2 was associated with the development of gastric cancer which might function as a potential therapeutic target for the disease.
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Affiliation(s)
- Xin Guo
- Department of Digestive Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi; Department of Digestive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoqian Bu
- Department of Digestive Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi; Department of Digestive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Yuan
- Department of Digestive Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi; Department of Digestive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lina Ji
- Department of Digestive Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi; Department of Digestive Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Liu Y, Wen H, Wang Q, Du S. Research trends in endoscopic applications in early gastric cancer: A bibliometric analysis of studies published from 2012 to 2022. Front Oncol 2023; 13:1124498. [PMID: 37114137 PMCID: PMC10129370 DOI: 10.3389/fonc.2023.1124498] [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: 12/15/2022] [Accepted: 03/13/2023] [Indexed: 04/29/2023] Open
Abstract
Background Endoscopy is the optimal method of diagnosing and treating early gastric cancer (EGC), and it is therefore important to keep up with the rapid development of endoscopic applications in EGC. This study utilized bibliometric analysis to describe the development, current research progress, hotspots, and emerging trends in this field. Methods We retrieved publications about endoscopic applications in EGC from 2012 to 2022 from Web of Science™ (Clarivate™, Philadelphia, PA, USA) Core Collection (WoSCC). We mainly used CiteSpace (version 6.1.R3) and VOSviewer (version 1.6.18) to perform the collaboration network analysis, co-cited analysis, co-occurrence analysis, cluster analysis, and burst detection. Results A total of 1,333 publications were included. Overall, both the number of publications and the average number of citations per document per year increased annually. Among the 52 countries/regions that were included, Japan contributed the most in terms of publications, citations, and H-index, followed by the Republic of Korea and China. The National Cancer Center, based in both Japan and the Republic of Korea, ranked first among institutions in terms of number of publications, citation impact, and the average number of citations. Yong Chan Lee was the most productive author, and Ichiro Oda had the highest citation impact. In terms of cited authors, Gotoda Takuji had both the highest citation impact and the highest centrality. Among journals, Surgical Endoscopy and Other Interventional Techniques had the most publications, and Gastric Cancer had the highest citation impact and H-index. Among all publications and cited references, a paper by Smyth E C et al., followed by one by Gotoda T et al., had the highest citation impact. Using keywords co-occurrence and cluster analysis, 1,652 author keywords were categorized into 26 clusters, and we then divided the clusters into six groups. The largest and newest clusters were endoscopic submucosal dissection and artificial intelligence (AI), respectively. Conclusions Over the last decade, research into endoscopic applications in EGC has gradually increased. Japan and the Republic of Korea have contributed the most, but research in this field in China, from an initially low base, is developing at a striking speed. However, a lack of collaboration among countries, institutions, and authors, is common, and this should be addressed in future. The main focus of research in this field (i.e., the largest cluster) is endoscopic submucosal dissection, and the topic at the frontier (i.e., the newest cluster) is AI. Future research should focus on the application of AI in endoscopy, and its implications for the clinical diagnosis and treatment of EGC.
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Affiliation(s)
- Yuan Liu
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Haolang Wen
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Qiao Wang
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Shiyu Du,
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Xu W, Ding H, Zhang M, Liu L, Yin M, Weng Z, Xu C. The prognostic role of fatty acid metabolism-related genes in patients with gastric cancer. Transl Cancer Res 2022; 11:3593-3609. [PMID: 36388036 PMCID: PMC9641091 DOI: 10.21037/tcr-22-761] [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: 03/20/2022] [Accepted: 08/02/2022] [Indexed: 08/30/2023]
Abstract
BACKGROUND With the deepening research on fatty acid metabolism, people have achieved a preliminary understanding of it in the development and prognosis of tumors. However, few studies are still on the expression pattern and prognostic value of fatty acid metabolism-related genes in gastric cancer (GC). METHODS We chose 93 genes relevant to fatty acid metabolism from the Gene Set Enrichment Analysis (GSEA) database. We analyzed differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA) patients. Univariate Cox analysis and LASSO regression were used to select the genes most related to prognosis and therefore developed a prognosis model. In addition, a dataset of 76 samples from Gene Expression Omnibus (GEO) selected as a test set to aid in the development of a prognostic model. The prognostic relevance of this model was confirmed using Kaplan-Meier survival analysis, univariate/multivariate Cox analysis, and receiver operating characteristic (ROC) curve. Finally, enrichment analysis and protein-protein interaction (PPI) were used to analyze the functional differences of patients with different risk. Immune infiltration analysis based on CIBERSORT could check the infiltration degree and immune function changes of immune cell subtypes in patients with different risk groups. RESULTS Overexpression of ELOVL4, ADH4, CPT1C, and ADH1B was linked to poor overall survival (OS) in GC patients, according to our findings. Furthermore, according to prognostic factors, patients with lower risk score tend to have better prognosis than patients with higher risk score. In addition, we also found that the infiltration levels of B cells, dendritic cells, auxiliary T cells, mast cells, neutrophils and tumor-infiltrating lymphocytes in patients with high-risk group were significantly increased, and the type II IFN response of immune cells, CCR and MHC class I receptor functions were significantly enhanced, suggesting that the tumor microenvironment immune activity in patients with high-risk group was active. CONCLUSIONS Four fatty acid metabolism-related genes were discovered to be closely connected to the prognosis of individuals with GC. Through analysis and verification, we believed that this prognostic model was reliable and instructive in the prediction of the prognosis of GC.
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Affiliation(s)
- Wei Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - He Ding
- Cyrus Tang Hematology Center, Soochow University, Suzhou, China
| | - Man Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Minyue Yin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhen Weng
- Cyrus Tang Hematology Center and Ministry of Education Engineering Center of Hematological Disease, and the Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Chunfang Xu
- The First Affiliated Hospital of Soochow University, Suzhou, China
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Comparing Different Anesthesia Methods on Anesthetic Effect and Postoperative Pain in Patients with Early Gastric Cancer during Endoscopic Submucosal Dissection. JOURNAL OF ONCOLOGY 2022; 2022:7299360. [PMID: 36072967 PMCID: PMC9444400 DOI: 10.1155/2022/7299360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/18/2022] [Accepted: 08/06/2022] [Indexed: 11/17/2022]
Abstract
Endoscopic submucosal dissection (ESD) is a minimally invasive technique to completely peel the pathological mucosa from the submucosa under endoscopy, which has been often utilized to treat early gastric cancer. During the operation, anesthesia is required to reduce the discomfort due to the complexity, high risk, and longtime operation of ESD. In this study, we compared different anesthesia methods on anesthetic effect and postoperative pain in patients (≥65 years old) with early gastric cancer during ESD. For this purpose, 60 patients with early gastric cancer who were more than 65 years old were selected from January 2019 to December 2021, where 30 patients treated with simple intravenous general anesthesia were divided into the simple group and 30 patients treated with intravenous combined inhalation general anesthesia were regarded as the composite group. The hemodynamic index, wake-up time, postoperative pain intensity, operation time, and the incidence of adverse reactions were compared between the two groups. For the hemodynamic index before incision, after incision, and at the end of the operation, the mean arterial pressure (MAP) in the composite group was higher than that in the simple group (P < 0.05) and the heart rate (HR) was lower than that in the simple group (P < 0.05). After the ESD operation, the wake-up time and visual analogue scale (VAS) in the composite group were lower than those in the simple group (P < 0.05). In addition, the ESD operation time and incidence of adverse reactions in the composite group was significantly lower than that in the simple group (P < 0.05). These results showed that intravenous combined inhalation general anesthesia had a good anesthetic effect, stable hemodynamics during ESD operation, and slight postoperative pain.
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SLC6A14 Depletion Contributes to Amino Acid Starvation to Suppress EMT-Induced Metastasis in Gastric Cancer by Perturbing the PI3K/AKT/mTORC1 Pathway. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7850658. [PMID: 35865664 PMCID: PMC9296317 DOI: 10.1155/2022/7850658] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 05/10/2022] [Accepted: 05/20/2022] [Indexed: 11/18/2022]
Abstract
Metastasis is the main obstacle for the treatment of gastric cancer (GC), leading to low survival rate and adverse outcomes in CG patients. SLC6A14, a general amino acid transporter, can import all the essential amino acids in a manner dependent on the NaCl-generated osmotic gradients. Herein, we constructed GC cell sublines with high (SGC7901-M and MKN28-M) and low (MKN28-NM and SGC7901-NM) metastatic ability. Putative functional genes advancing GC metastasis were identified using mRNA microarray analysis and High-Content Screening. In particular, most significant change with a dampening trend in the migration potentiality of GC cells emerged after SLC6A14 gene was silenced. SLC6A14 expression was positively correlated with the migrated capability of different GC cell lines, and SLC6A14 was also constitutively expressed in GC patients with venous or lymphatic invasion, lymph node, or distant metastasis and poor prognosis, thus prompting SLC6A14 as a nonnegligible presence in supporting GC migration and invasion. Consistently, SLC6A14 depletion drastically depressed GC metastasis in vitro and in vivo. Most importantly, pharmacological blockade and gene silence of SLC6A14 both restricted epithelial-mesenchymal transition- (EMT-) driven GC metastasis, in which attenuated activation of the PI3K/AKT/mTORC1 pathway caused by amino acid starvation was involved. In summary, it is conceivable that targeting SLC6A14 has a tremendous promising for the treatment of metastatic GC.
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The global, regional and national burden of stomach cancer and its attributable risk factors from 1990 to 2019. Sci Rep 2022; 12:11542. [PMID: 35798837 PMCID: PMC9262989 DOI: 10.1038/s41598-022-15839-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 06/30/2022] [Indexed: 12/12/2022] Open
Abstract
We aimed to estimate the incidence, mortality, and disability-adjusted life-years (DALYs) of stomach cancer at the global, regional, and national levels. Stomach cancer resulted in 1.3 million (1.2-1.4 million) incident cases, 9.5 hundred thousand (8.7-10.4 hundred thousand) deaths, and 22.2 million (20.3-24.1 million) DALYs in 2019. The age-standardized incidence rate, death rate and DALY rate were 15.6 (14.1-17.2), 11.9 (10.8-12.8), and 268.4 (245.5-290.6) per 100,000 person-years, respectively. Between 1990 and 2019, the global age-standardized incidence rate, death rate, and DALY rate decreased by - 30.5% (- 36.7 to - 22.9), - 41.9% (- 47.2 to - 36.3), and - 45.6% (- 50.8 to - 39.8), respectively. In 2019, most of the global numbers of incidence, death and DALYs were higher among males than females. A considerable burden of stomach cancer was attributable to smoking and a high-sodium diet. Although the global age-standardized incidence and death rates have decreased, continued growth in absolute numbers in some regions, especially in East Asia, poses a major global public health challenge. To address this, public health responses should be tailored to fit each country's unique situation. Primary and secondary prevention strategies with increased effectiveness are required to reduce the incidence and mortality of stomach cancer, particularly in populations with a high disease burden.
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Wei J, Li J, Geng D, Peng Y, Yang B, Wu H, Zhou Y. Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients. Front Surg 2022; 9:897583. [PMID: 35592126 PMCID: PMC9110967 DOI: 10.3389/fsurg.2022.897583] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/08/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients. Methods A total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended. Results The relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05). Conclusion The expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.
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Chiarello MM, Fico V, Pepe G, Tropeano G, Adams NJ, Altieri G, Brisinda G. Early gastric cancer: A challenge in Western countries. World J Gastroenterol 2022; 28:693-703. [PMID: 35317273 PMCID: PMC8891729 DOI: 10.3748/wjg.v28.i7.693] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/04/2022] [Accepted: 01/22/2022] [Indexed: 02/06/2023] Open
Abstract
Early gastric cancer (EGC) is an invasive carcinoma involving only the stomach mucosa or submucosa, independently of lymph node status. EGC represents over 50% of cases in Japan and in South Korea, whereas it accounts only for approximately 20% of all newly diagnosed gastric cancers in Western countries. The main classification systems of EGC are the Vienna histopathologic classification and the Paris endoscopic classification of polypoid and non-polypoid lesions. A careful endoscopic assessment is fundamental to establish the best treatment of EGC. Generally, EGCs are curable if the lesion is completely removed by endoscopic resection or surgery. Some types of EGC can be resected endoscopically; for others the most appropriate treatment is surgical resection and D2 lymphadenectomy, especially in Western countries. The favorable oncological prognosis, the extended lymphadenectomy and the reconstruction of the intestinal continuity that excludes the duodenum make the prophylactic cholecystectomy mandatory to avoid the onset of biliary complications.
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Affiliation(s)
- Maria Michela Chiarello
- Department of Surgery, Azienda Sanitaria Provinciale di Crotone, Ospedale San Giovanni di Dio, Crotone 88900, Italy
| | - Valeria Fico
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Gilda Pepe
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Tropeano
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Neill James Adams
- Health Sciences, Clinical Microbiology Unit, Magna Grecia University, Catanzaro 88100, Italy
| | - Gaia Altieri
- Emergency Surgery and Trauma Center, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
| | - Giuseppe Brisinda
- Department of Medical and Surgical Sciences, Catholic School of Medicine, Rome 00168, Italy
- Department of Surgery, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
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