{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:18:06Z","timestamp":1775063886472,"version":"3.50.1"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Science and Technology Foundation of Panyu","award":["2022-Z04-095"],"award-info":[{"award-number":["2022-Z04-095"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802342"],"award-info":[{"award-number":["81802342"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kelin New Star Project of the First Affiliated Hospital of Sun Yat\u2010sen University","award":["R08010"],"award-info":[{"award-number":["R08010"]}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2023A04J2208"],"award-info":[{"award-number":["2023A04J2208"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"DOI":"10.1186\/s12916-025-04357-8","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:56:50Z","timestamp":1759312610000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["DNA methylation profiles predicting response to anti-PD-1-based treatment in patients with advanced gastric cancer"],"prefix":"10.1186","volume":"23","author":[{"given":"Wei","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuangqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"issue":"3","key":"4357_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA Cancer J Clin"},{"key":"4357_CR2","first-page":"101404","volume":"47","author":"E Morgan","year":"2022","unstructured":"Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, Matsuda T, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020\u201340: a population-based modelling study. EClin Med. 2022;47:101404.","journal-title":"EClin Med"},{"issue":"1","key":"4357_CR3","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13045-024-01578-x","volume":"17","author":"X Chong","year":"2024","unstructured":"Chong X, Madeti Y, Cai J, Li W, Cong L, Lu J, et al. Recent developments in immunotherapy for gastrointestinal tract cancers. J Hematol Oncol. 2024;17(1):65.","journal-title":"J Hematol Oncol"},{"issue":"10294","key":"4357_CR4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","volume":"398","author":"YY Janjigian","year":"2021","unstructured":"Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27\u201340.","journal-title":"Lancet"},{"issue":"21","key":"4357_CR5","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1001\/jama.2023.19918","volume":"330","author":"J Xu","year":"2023","unstructured":"Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial. JAMA. 2023;330(21):2064\u201374.","journal-title":"JAMA"},{"issue":"2","key":"4357_CR6","doi-asserted-by":"publisher","first-page":"167","DOI":"10.6004\/jnccn.2022.0008","volume":"20","author":"J Ajani","year":"2022","unstructured":"Ajani J, D'Amico T, Bentrem D, Chao J, Cooke D, Corvera C, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Nat Compr Cancer Net : JNCCN. 2022;20(2):167\u201392.","journal-title":"J Nat Compr Cancer Net : JNCCN"},{"issue":"2","key":"4357_CR7","doi-asserted-by":"publisher","first-page":"102226","DOI":"10.1016\/j.esmoop.2023.102226","volume":"9","author":"K Shitara","year":"2024","unstructured":"Shitara K, Fleitas T, Kawakami H, Curigliano G, Narita Y, Wang F, et al. Pan-Asian adapted ESMO clinical practice guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer. ESMO Open. 2024;9(2):102226.","journal-title":"ESMO Open"},{"issue":"6","key":"4357_CR8","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1158\/2159-8290.CD-20-1312","volume":"11","author":"D Salas-Benito","year":"2021","unstructured":"Salas-Benito D, P\u00e9rez-Gracia JL, Ponz-Sarvis\u00e9 M, Rodriguez-Ruiz ME, Mart\u00ednez-Forero I, Casta\u00f1\u00f3n E, et al. Paradigms on immunotherapy combinations with chemotherapy. Cancer Discov. 2021;11(6):1353\u201367.","journal-title":"Cancer Discov"},{"issue":"4","key":"4357_CR9","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s10120-020-01090-4","volume":"23","author":"K Kono","year":"2020","unstructured":"Kono K, Nakajima S, Mimura K. Current status of immune checkpoint inhibitors for gastric cancer. Gastric Cancer. 2020;23(4):565\u201378.","journal-title":"Gastric Cancer"},{"issue":"21","key":"4357_CR10","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.3748\/wjg.v30.i21.2734","volume":"30","author":"SY Yan","year":"2024","unstructured":"Yan SY, Fan JG. Application of immune checkpoint inhibitors and microsatellite instability in gastric cancer. World J Gastroenterol. 2024;30(21):2734\u20139.","journal-title":"World J Gastroenterol"},{"issue":"9","key":"4357_CR11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11912-018-0718-6","volume":"20","author":"DJ Palmieri","year":"2018","unstructured":"Palmieri DJ, Carlino MS. Immune checkpoint inhibitor toxicity. Curr Oncol Rep. 2018;20(9):72.","journal-title":"Curr Oncol Rep"},{"key":"4357_CR12","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000791","author":"BW Kang","year":"2020","unstructured":"Kang BW, Chau I. Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer. ESMO Open. 2020. https:\/\/doi.org\/10.1136\/esmoopen-2020-000791.","journal-title":"ESMO Open"},{"issue":"21","key":"4357_CR13","doi-asserted-by":"publisher","first-page":"e29304","DOI":"10.1097\/MD.0000000000029304","volume":"101","author":"X Chang","year":"2022","unstructured":"Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022;101(21):e29304.","journal-title":"Medicine (Baltimore)"},{"issue":"12","key":"4357_CR14","doi-asserted-by":"publisher","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","volume":"17","author":"GT Gibney","year":"2016","unstructured":"Gibney GT, Weiner LM, Atkins MB. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 2016;17(12):e542\u201351.","journal-title":"Lancet Oncol"},{"issue":"3","key":"4357_CR15","doi-asserted-by":"publisher","first-page":"e460","DOI":"10.1634\/theoncologist.2019-0471","volume":"25","author":"M Di Bartolomeo","year":"2020","unstructured":"Di Bartolomeo M, Morano F, Raimondi A, Miceli R, Corallo S, Tamborini E, et al. Prognostic and predictive value of microsatellite instability, inflammatory reaction and PD-L1 in gastric cancer patients treated with either adjuvant 5-FU\/LV or sequential FOLFIRI followed by cisplatin and docetaxel: a translational analysis from the ITACA-S trial. Oncologist. 2020;25(3):e460\u20138.","journal-title":"Oncologist"},{"issue":"4","key":"4357_CR16","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/s10120-022-01301-0","volume":"25","author":"J Yeong","year":"2022","unstructured":"Yeong J, Lum HYJ, Teo CB, Tan BKJ, Chan YH, Tay RYK, et al. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric Cancer. 2022;25(4):741\u201350.","journal-title":"Gastric Cancer"},{"key":"4357_CR17","doi-asserted-by":"publisher","first-page":"1377690","DOI":"10.3389\/fphar.2024.1377690","volume":"15","author":"F Zhang","year":"2024","unstructured":"Zhang F, Chen G, Yin Y, Chen X, Nie R, Chen Y. First-line immune checkpoint inhibitors in low programmed death-ligand 1-expressing population. Front Pharmacol. 2024;15:1377690.","journal-title":"Front Pharmacol"},{"issue":"7517","key":"4357_CR18","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nature13480","volume":"513","author":"Comprehensive molecular characterization of gastric adenocarcinoma","year":"2014","unstructured":"Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202\u20139.","journal-title":"Nature"},{"key":"4357_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7090305","author":"A Yanagi","year":"2019","unstructured":"Yanagi A, Nishikawa J, Shimokuri K, Shuto T, Takagi T, Takagi F, et al. Clinicopathologic characteristics of Epstein-Barr virus-associated gastric cancer over the past decade in Japan. Microorganisms. 2019. https:\/\/doi.org\/10.3390\/microorganisms7090305.","journal-title":"Microorganisms"},{"issue":"2","key":"4357_CR20","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41588-018-0312-8","volume":"51","author":"RM Samstein","year":"2019","unstructured":"Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202\u20136.","journal-title":"Nat Genet"},{"issue":"2","key":"4357_CR21","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1470-2045(22)00783-5","volume":"24","author":"J Wang","year":"2023","unstructured":"Wang J, Xiu J, Farrell A, Baca Y, Arai H, Battaglin F, et al. Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study. Lancet Oncol. 2023;24(2):151\u201361.","journal-title":"Lancet Oncol"},{"issue":"1","key":"4357_CR22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/npp.2012.112","volume":"38","author":"LD Moore","year":"2013","unstructured":"Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013;38(1):23\u201338.","journal-title":"Neuropsychopharmacology"},{"issue":"6","key":"4357_CR23","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1042\/EBC20190030","volume":"63","author":"A Angeloni","year":"2019","unstructured":"Angeloni A, Bogdanovic O. Enhancer DNA methylation: implications for gene regulation. Essays Biochem. 2019;63(6):707\u201315.","journal-title":"Essays Biochem"},{"key":"4357_CR24","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1146\/annurev.pharmtox.45.120403.095832","volume":"45","author":"M Esteller","year":"2005","unstructured":"Esteller M. Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol. 2005;45:629\u201356.","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"4357_CR25","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/978-94-007-4525-4_26","volume":"61","author":"G Gokul","year":"2013","unstructured":"Gokul G, Khosla S. DNA methylation and cancer. Subcell Biochem. 2013;61:597\u2013625.","journal-title":"Subcell Biochem"},{"issue":"2","key":"4357_CR26","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1373\/clinchem.2007.095992","volume":"54","author":"C Lofton-Day","year":"2008","unstructured":"Lofton-Day C, Model F, Devos T, Tetzner R, Distler J, Schuster M, et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem. 2008;54(2):414\u201323.","journal-title":"Clin Chem"},{"issue":"7","key":"4357_CR27","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1200\/JCO.2016.68.2153","volume":"35","author":"J Qiu","year":"2017","unstructured":"Qiu J, Peng B, Tang Y, Qian Y, Guo P, Li M, et al. Cpg methylation signature predicts recurrence in early-stage hepatocellular carcinoma: results from a multicenter study. J Clin Oncol. 2017;35(7):734\u201342.","journal-title":"J Clin Oncol"},{"issue":"10","key":"4357_CR28","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/S2213-2600(18)30284-4","volume":"6","author":"M Duruisseaux","year":"2018","unstructured":"Duruisseaux M, Mart\u00ednez-Card\u00fas A, Calleja-Cervantes ME, Moran S, Castro de Moura M, Davalos V, et al. Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicentre, retrospective analysis. Lancet Respir Med. 2018;6(10):771\u201381.","journal-title":"Lancet Respir Med"},{"key":"4357_CR29","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003420","author":"AM Starzer","year":"2022","unstructured":"Starzer AM, Heller G, Tomasich E, Melchardt T, Feldmann K, Hatziioannou T, et al. DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma. J Immunother Cancer. 2022. https:\/\/doi.org\/10.1136\/jitc-2021-003420.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"4357_CR30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ccell.2021.11.012","volume":"40","author":"F Newell","year":"2022","unstructured":"Newell F, Pires da Silva I, Johansson PA, Menzies AM, Wilmott JS, Addala V, et al. Multiomic profiling of checkpoint inhibitor-treated melanoma: identifying predictors of response and resistance, and markers of biological discordance. Cancer Cell. 2022;40(1):88\u2013102.e7.","journal-title":"Cancer Cell"},{"key":"4357_CR31","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001458","author":"AM Starzer","year":"2021","unstructured":"Starzer AM, Berghoff AS, Hamacher R, Tomasich E, Feldmann K, Hatziioannou T, et al. Tumor DNA methylation profiles correlate with response to anti-PD-1 immune checkpoint inhibitor monotherapy in sarcoma patients. J Immunother Cancer. 2021. https:\/\/doi.org\/10.1136\/jitc-2020-001458.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"4357_CR32","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13148-023-01525-6","volume":"15","author":"F Hoffmann","year":"2023","unstructured":"Hoffmann F, Franzen A, de Vos L, Wuest L, Kulcs\u00e1r Z, Fietz S, et al. CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma. Clin Epigenetics. 2023;15(1):112.","journal-title":"Clin Epigenetics"},{"issue":"2","key":"4357_CR33","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228\u201347.","journal-title":"Eur J Cancer"},{"issue":"24","key":"4357_CR34","doi-asserted-by":"publisher","first-page":"3982","DOI":"10.1093\/bioinformatics\/btx513","volume":"33","author":"Y Tian","year":"2017","unstructured":"Tian Y, Morris TJ, Webster AP, Yang Z, Beck S, Feber A, et al. ChAMP: updated methylation analysis pipeline for Illumina BeadChips. Bioinformatics. 2017;33(24):3982\u20134.","journal-title":"Bioinformatics"},{"issue":"2","key":"4357_CR35","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/bioinformatics\/bts680","volume":"29","author":"AE Teschendorff","year":"2013","unstructured":"Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2013;29(2):189\u201396.","journal-title":"Bioinformatics"},{"issue":"1","key":"4357_CR36","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","volume":"8","author":"WE Johnson","year":"2007","unstructured":"Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118\u201327.","journal-title":"Biostatistics"},{"issue":"W1","key":"4357_CR37","doi-asserted-by":"publisher","first-page":"W415","DOI":"10.1093\/nar\/gkae456","volume":"52","author":"JM Elizarraras","year":"2024","unstructured":"Elizarraras JM, Liao Y, Shi Z, Zhu Q, Pico AR, Zhang B. Webgestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics. Nucleic Acids Res. 2024;52(W1):W415\u201321.","journal-title":"Nucleic Acids Res"},{"issue":"15","key":"4357_CR38","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114\u201320.","journal-title":"Bioinformatics"},{"key":"4357_CR39","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-10-232","volume":"10","author":"Y Xi","year":"2009","unstructured":"Xi Y, Li W. Bsmap: whole genome bisulfite sequence mapping program. BMC Bioinformatics. 2009;10:232.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"4357_CR40","first-page":"795624","volume":"2014","author":"M-L Huang","year":"2014","unstructured":"Huang M-L, Hung Y-H, Lee W, Li R-K, Jiang B-R. SVM-rfe based feature selection and Taguchi parameters optimization for multiclass SVM classifier. Sci World J. 2014;2014(1):795624.","journal-title":"Sci World J"},{"issue":"1","key":"4357_CR41","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","volume":"58","author":"R Tibshirani","year":"1996","unstructured":"Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Ser B Stat Methodol. 1996;58(1):267\u201388.","journal-title":"J R Stat Soc Ser B Stat Methodol"},{"issue":"10","key":"4357_CR42","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41551-018-0304-0","volume":"2","author":"SM Lundberg","year":"2018","unstructured":"Lundberg SM, Nair B, Vavilala MS, Horibe M, Eisses MJ, Adams T, et al. Explainable machine-learning predictions for the prevention of hypoxaemia during surgery. Nat Biomed Eng. 2018;2(10):749\u201360.","journal-title":"Nat Biomed Eng"},{"key":"4357_CR43","unstructured":"Lundberg SM, Lee S-I. A unified approach to interpreting model predictions. Advances in neural information processing systems. 2017;30."},{"key":"4357_CR44","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1016\/j.csbj.2024.06.035","volume":"23","author":"H Liu","year":"2024","unstructured":"Liu H, Zhang W, Zhang Y, Adegboro AA, Fasoranti DO, Dai L, et al. Mime: a flexible machine-learning framework to construct and visualize models for clinical characteristics prediction and feature selection. Comput Struct Biotechnol J. 2024;23:2798\u2013810.","journal-title":"Comput Struct Biotechnol J"},{"issue":"Pt A","key":"4357_CR45","doi-asserted-by":"publisher","first-page":"109317","DOI":"10.1016\/j.intimp.2022.109317","volume":"113","author":"M Noori","year":"2022","unstructured":"Noori M, Mahjoubfar A, Azizi S, Fayyaz F, Rezaei N. Immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric and esophageal cancers: a systematic review and meta-analysis. Int Immunopharmacol. 2022;113(Pt A):109317.","journal-title":"Int Immunopharmacol"},{"key":"4357_CR46","doi-asserted-by":"publisher","first-page":"153303382412732","DOI":"10.1177\/15330338241273286","volume":"23","author":"L Zhang","year":"2024","unstructured":"Zhang L, Huang L, Liu Z, Ling T. Immune checkpoint inhibitor plus chemotherapy as first-line treatment for advanced gastric or gastroesophageal junction cancer: a systematic review and meta-analysis. Technol Cancer Res Treat. 2024;23:15330338241273286.","journal-title":"Technol Cancer Res Treat"},{"key":"4357_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16152692","author":"M Ratti","year":"2024","unstructured":"Ratti M, Orlandi E, Toscani I, Vecchia S, Anselmi E, Hahne JC, et al. Emerging therapeutic targets and future directions in advanced gastric cancer: a comprehensive review. Cancers (Basel). 2024. https:\/\/doi.org\/10.3390\/cancers16152692.","journal-title":"Cancers (Basel)"},{"issue":"1","key":"4357_CR48","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1038\/s41467-022-32570-z","volume":"13","author":"Y Chen","year":"2022","unstructured":"Chen Y, Jia K, Sun Y, Zhang C, Li Y, Zhang L, et al. Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment. Nat Commun. 2022;13(1):4851.","journal-title":"Nat Commun"},{"issue":"8","key":"4357_CR49","doi-asserted-by":"publisher","first-page":"101146","DOI":"10.1016\/j.xcrm.2023.101146","volume":"4","author":"Y Jiang","year":"2023","unstructured":"Jiang Y, Zhou K, Sun Z, Wang H, Xie J, Zhang T, et al. Non-invasive tumor microenvironment evaluation and treatment response prediction in gastric cancer using deep learning radiomics. Cell Rep Med. 2023;4(8):101146.","journal-title":"Cell Rep Med"},{"key":"4357_CR50","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-008927","author":"Z Han","year":"2024","unstructured":"Han Z, Zhang Z, Yang X, Li Z, Sang S, Islam MT, et al. Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer. J Immunother Cancer. 2024. https:\/\/doi.org\/10.1136\/jitc-2024-008927.","journal-title":"J Immunother Cancer"},{"issue":"4","key":"4357_CR51","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/s41419-022-04821-w","volume":"13","author":"L Zhao","year":"2022","unstructured":"Zhao L, Liu Y, Zhang S, Wei L, Cheng H, Wang J. Impacts and mechanisms of metabolic reprogramming of tumor microenvironment for immunotherapy in gastric cancer. Cell Death Dis. 2022;13(4):378.","journal-title":"Cell Death Dis"},{"issue":"2","key":"4357_CR52","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s11523-024-01041-4","volume":"19","author":"JM Ressler","year":"2024","unstructured":"Ressler JM, Tomasich E, Hatziioannou T, Ringl H, Heller G, Silmbrod R, et al. DNA methylation signatures correlate with response to immune checkpoint inhibitors in metastatic melanoma. Target Oncol. 2024;19(2):263\u201375.","journal-title":"Target Oncol"},{"issue":"1","key":"4357_CR53","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1083\/jcb.200807195","volume":"185","author":"F Sabeh","year":"2009","unstructured":"Sabeh F, Shimizu-Hirota R, Weiss SJ. Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol. 2009;185(1):11\u20139.","journal-title":"J Cell Biol"},{"key":"4357_CR54","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202308069","author":"F Peglion","year":"2024","unstructured":"Peglion F, Etienne-Manneville S. Cell polarity changes in cancer initiation and progression. J Cell Biol. 2024. https:\/\/doi.org\/10.1083\/jcb.202308069.","journal-title":"J Cell Biol"},{"issue":"6","key":"4357_CR55","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.ccell.2024.05.007","volume":"42","author":"N Layer","year":"2024","unstructured":"Layer N, Bunse L, Venkataramani V. Neural deception: breast cancer co-opts neuronal mechanisms to evade the immune system. Cancer Cell. 2024;42(6):936\u20138.","journal-title":"Cancer Cell"},{"issue":"7","key":"4357_CR56","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nrg3230","volume":"13","author":"PA Jones","year":"2012","unstructured":"Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484\u201392.","journal-title":"Nat Rev Genet"},{"key":"4357_CR57","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.semcancer.2019.08.018","volume":"60","author":"S Marx","year":"2020","unstructured":"Marx S, Dal Maso T, Chen JW, Bury M, Wouters J, Michiels C, et al. Transmembrane (TMEM) protein family members: poorly characterized even if essential for the metastatic process. Semin Cancer Biol. 2020;60:96\u2013106.","journal-title":"Semin Cancer Biol"},{"key":"4357_CR58","doi-asserted-by":"publisher","DOI":"10.3892\/or.2021.8127","author":"X Zhang","year":"2021","unstructured":"Zhang X, He Y, Jiang Y, Bao Y, Chen Q, Xie D, et al. TMEM229A suppresses non-small cell lung cancer progression via inactivating the ERK pathway. Oncol Rep. 2021. https:\/\/doi.org\/10.3892\/or.2021.8127.","journal-title":"Oncol Rep"},{"issue":"3","key":"4357_CR59","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1007\/s13402-024-00916-y","volume":"47","author":"K Peng","year":"2024","unstructured":"Peng K, Liu Y, Liu S, Wang Z, Zhang H, He W, et al. Targeting MEK\/COX-2 axis improve immunotherapy efficacy in dMMR colorectal cancer with PIK3CA overexpression. Cell Oncol (Dordr). 2024;47(3):1043\u201358.","journal-title":"Cell Oncol (Dordr)"},{"issue":"5","key":"4357_CR60","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1093\/neuonc\/noad248","volume":"26","author":"MA de Sauvage","year":"2024","unstructured":"de Sauvage MA, Torrini C, Nieblas-Bedolla E, Summers EJ, Sullivan E, Zhang BS, et al. The ERK inhibitor LY3214996 augments anti-PD-1 immunotherapy in preclinical mouse models of BRAFV600E melanoma brain metastasis. Neuro Oncol. 2024;26(5):889\u2013901.","journal-title":"Neuro Oncol"},{"issue":"3","key":"4357_CR61","first-page":"1455","volume":"25","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Yao J, Feng J, Wang S, Yang Z, Huang W, et al. Relationship between PRRX1, circulating tumor cells, and clinicopathological parameter in patients with gastric cancer. J buon. 2020;25(3):1455\u201362.","journal-title":"J buon"},{"issue":"7","key":"4357_CR62","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/s41417-021-00376-8","volume":"29","author":"S Park","year":"2022","unstructured":"Park S, Lee AY, Cho KC, Jung JH, Hong SH, Kim S, et al. FCH domain only 1 (FCHo1), a potential new biomarker for lung cancer. Cancer Gene Ther. 2022;29(7):901\u20137.","journal-title":"Cancer Gene Ther"},{"issue":"11","key":"4357_CR63","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1158\/0008-5472.CAN-22-0370","volume":"83","author":"AL Miller","year":"2023","unstructured":"Miller AL, Perurena N, Gardner A, Hinoue T, Loi P, Laird PW, et al. DAB2IP is a bifunctional tumor suppressor that regulates wild-type ras and inflammatory cascades in KRAS mutant colon cancer. Cancer Res. 2023;83(11):1800\u201314.","journal-title":"Cancer Res"},{"issue":"7534","key":"4357_CR64","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature14192","volume":"517","author":"D Sch\u00fcbeler","year":"2015","unstructured":"Sch\u00fcbeler D. Function and information content of DNA methylation. Nature. 2015;517(7534):321\u20136.","journal-title":"Nature"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04357-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-025-04357-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04357-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T11:05:15Z","timestamp":1759316715000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/s12916-025-04357-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4357"],"URL":"https:\/\/doi.org\/10.1186\/s12916-025-04357-8","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]},"assertion":[{"value":"12 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and reviewed and approved by the Ethics Committee for Clinical Research and Animal Trials of the First Affiliated Hospital of Sun Yat-sen University (Approval No. [2022]715). Written consent was obtained from all participants involved in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"529"}}