{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:23:09Z","timestamp":1787664189025,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cDunarea de Jos\u201d University, Faculty of Medicine and Pharmacy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Gastric Cancer (GC) is characterized by remarkable biological heterogeneity, reflected by the continuous expansion of biomarkers with diagnostic, prognostic, predictive, and therapeutic relevance. However, most reviews organize these biomarkers according to signaling pathways or individual molecular alterations, often overlooking the interconnected biological processes and functional states that shape gastric carcinogenesis and tumor evolution. This review proposes a biology-oriented conceptual framework that interprets GC biomarkers through five fundamental biological questions capturing interconnected biological capabilities and tumor states: preservation of gastric lineage identity, acquisition of stem cell-like properties, epithelial\u2013mesenchymal transition, immune evasion, and dependence on actionable oncogenic pathways. Within each biological domain, biomarkers were critically selected and comparatively evaluated according to their biological significance, pathological applicability, translational relevance, and clinical utility. Core biomarkers central to each biological process are discussed alongside complementary biomarkers that further refine biological interpretation and clinical stratification. Rather than presenting another comprehensive catalogue of molecular alterations, this review integrates current evidence into a coherent framework linking tumor biology with diagnostic pathology and precision oncology. By emphasizing biological capabilities rather than isolated molecular pathways, this approach provides a practical perspective for biomarker interpretation and establishes a conceptual foundation for future multimarker strategies in GC.<\/jats:p>","DOI":"10.3390\/cancers18172757","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:57:17Z","timestamp":1787662637000},"page":"2757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastric Cancer Biomarkers: From Cellular Identity to Precision Oncology"],"prefix":"10.3390","volume":"18","author":[{"given":"Catalin-Bogdan","family":"Satala","sequence":"first","affiliation":[{"name":"Medical and Pharmaceutical Research Center, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"},{"name":"Department of Pathology, Clinical County Emergency Hospital Braila, 810325 Braila, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina-Mihaela","family":"Gurau","sequence":"additional","affiliation":[{"name":"The School for Doctoral Studies in Biomedical Sciences, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Patrichi","sequence":"additional","affiliation":[{"name":"The Doctoral School of Medicine and Pharmacy, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-1364","authenticated-orcid":false,"given":"Gabriela","family":"Gurau","sequence":"additional","affiliation":[{"name":"Medical and Pharmaceutical Research Center, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"},{"name":"\u201cSf. Ioan\u201d Clinical Emergency Pediatric Hospital, 800487 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Cristina","family":"Mehedinti","sequence":"additional","affiliation":[{"name":"Medical and Pharmaceutical Research Center, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Mihalache","sequence":"additional","affiliation":[{"name":"Medical and Pharmaceutical Research Center, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 800008 Galati, Romania"},{"name":"Department of Pathology, Clinical County Emergency Hospital Braila, 810325 Braila, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s12276-023-00989-z","article-title":"Clinical Molecular Subtyping Reveals Intrinsic Mesenchymal Reprogramming in Gastric Cancer Cells","volume":"55","author":"Jang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3892\/or.2024.8847","article-title":"Role and Value of the Tumor Microenvironment in the Progression and Treatment Resistance of Gastric Cancer (Review)","volume":"53","author":"Yun","year":"2025","journal-title":"Oncol. Rep."},{"key":"ref_3","first-page":"212","article-title":"Advances and Challenges in Gastric Cancer Testing: The Role of Biomarkers","volume":"22","author":"Sun","year":"2025","journal-title":"Cancer Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sato, Y., Okamoto, K., Kawano, Y., Kasai, A., Kawaguchi, T., Sagawa, T., Sogabe, M., Miyamoto, H., and Takayama, T. (2023). Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144646"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41698-022-00251-1","article-title":"Single-Cell Analysis of Gastric Pre-Cancerous and Cancer Lesions Reveals Cell Lineage Diversity and Intratumoral Heterogeneity","volume":"6","author":"Kim","year":"2022","journal-title":"npj Precis. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1158\/2159-8290.CD-21-0683","article-title":"Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer","volume":"12","author":"Kumar","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Satala, C.B., Kovacs, Z., Bara, T., Jung, I., and Gurzu, S. (2023). Signet-Ring Cell Squamous Cell Carcinoma: A Biphenotypic Neoplasm of the Gastro-Esophageal Junction with Uncertain Biological Potential: Case Report and Literature Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119535"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1007\/s10120-024-01518-1","article-title":"Global Prevalence of Claudin 18 Isoform 2 in Tumors of Patients with Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma","volume":"27","author":"Shitara","year":"2024","journal-title":"Gastric Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16241","DOI":"10.1038\/s41598-022-19883-1","article-title":"V-Set and Immunoglobulin Domain Containing 1 (VSIG1) as an Emerging Target for Epithelial-Mesenchymal Transition of Gastric Cancer","volume":"12","author":"Satala","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1111\/cas.16282","article-title":"The Role of Gastric Mucins and Mucin-related Glycans in Gastric Cancers","volume":"115","author":"Arai","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7624","DOI":"10.1158\/1078-0432.CCR-08-1547","article-title":"Claudin-18 Splice Variant 2 Is a Pan-Cancer Target Suitable for Therapeutic Antibody Development","volume":"14","author":"Sahin","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00428-019-02624-7","article-title":"Expression of the Potential Therapeutic Target Claudin-18.2 Is Frequently Decreased in Gastric Cancer: Results from a Large Caucasian Cohort Study","volume":"475","author":"Dottermusch","year":"2019","journal-title":"Virchows Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40364-022-00385-1","article-title":"Claudin18.2 Is a Novel Molecular Biomarker for Tumor-Targeted Immunotherapy","volume":"10","author":"Cao","year":"2022","journal-title":"Biomark. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"oyae238","DOI":"10.1093\/oncolo\/oyae238","article-title":"Clinicopathologic and Molecular Characterization of Stages II-IV Gastric Cancer with Claudin 18.2 Expression","volume":"30","author":"Kwak","year":"2025","journal-title":"Oncologist"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pellino, A., Brignola, S., Riello, E., Niero, M., Murgioni, S., Guido, M., Nappo, F., Businello, G., Sbaraglia, M., and Bergamo, F. (2021). Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas. J. Pers. Med., 11.","DOI":"10.3390\/jpm11111095"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.annonc.2021.02.005","article-title":"FAST: A Randomised Phase II Study of Zolbetuximab (IMAB362) plus EOX versus EOX Alone for First-Line Treatment of Advanced CLDN18.2-Positive Gastric and Gastro-Oesophageal Adenocarcinoma","volume":"32","author":"Sahin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0140-6736(23)00620-7","article-title":"Zolbetuximab plus mFOLFOX6 in Patients with CLDN18.2-Positive, HER2-Negative, Untreated, Locally Advanced Unresectable or Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma (SPOTLIGHT): A Multicentre, Randomised, Double-Blind, Phase 3 Trial","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma: The Randomized, Phase 3 GLOW Trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100762","DOI":"10.1016\/j.esmoop.2022.100762","article-title":"Comprehensive Clinical and Molecular Characterization of Claudin 18.2 Expression in Advanced Gastric or Gastroesophageal Junction Cancer","volume":"8","author":"Kubota","year":"2023","journal-title":"ESMO Open"},{"key":"ref_20","first-page":"2","article-title":"Glycoprotein A34, a Novel Target for Antibody-Based Cancer Immunotherapy","volume":"6","author":"Scanlan","year":"2006","journal-title":"Cancer Immun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Oidovsambuu, O., Nyamsuren, G., Liu, S., G\u00f6ring, W., Engel, W., and Adham, I.M. (2011). Adhesion Protein VSIG1 Is Required for the Proper Differentiation of Glandular Gastric Epithelia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025908"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/jso.22150","article-title":"Decreased Expression of V-Set and Immunoglobulin Domain Containing 1 (VSIG1) Is Associated with Poor Prognosis in Primary Gastric Cancer","volume":"106","author":"Chen","year":"2012","journal-title":"J. Surg. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1111\/cas.13295","article-title":"Characterization of V-Set and Immunoglobulin Domain Containing 1 Exerting a Tumor Suppressor Function in Gastric, Lung, and Esophageal Cancer Cells","volume":"108","author":"Inoue","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Satala, C.-B., Jung, I., and Gurzu, S. (2023). Mucin-Phenotype and Expression of the Protein V-Set and Immunoglobulin Domain Containing 1 (VSIG1): New Insights into Gastric Carcinogenesis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108697"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Satala, C.-B., Gurau, A.-M., Mihalache, D., Patrichi, G., Mehedinti, R.-C., Leibovici, A.R., and Gur\u0103u, G. (2026). From Primary Tumor to Peritoneal Niche: Microenvironmental Divergence in Gastric Cancer Peritoneal Metastasis. Cells, 15.","DOI":"10.3390\/cells15121055"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Satala, C.-B., Patrichi, G., Gurau, A.-M., Onofrei Popa, A., and Mihalache, D. (2026). Beyond Gastric Specificity: V-Set and Immunoglobulin Domain-Containing 1 (VSIG1) in Digestive Tract Tumors. Cancers, 18.","DOI":"10.3390\/cancers18050867"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lutz, F., Han, S.-Y., B\u00fcy\u00fccek, S., M\u00f6ller, K., Viehweger, F., Schlichter, R., Menz, A., Luebke, A.M., Bawahab, A.A., and Reiswich, V. (2024). Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors. Diagnostics, 14.","DOI":"10.3390\/diagnostics14192157"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"E, Y., Yu, Q., Sun, T., Xue, H., Zhao, X.-R., and Zheng, H.-C. (2023). The Relationship between Pepsinogen C and Gastric Carcinogenesis: A Transgene and Population Study. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11020-z"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zaarour, R.F., Ribeiro, M., Azzarone, B., Kapoor, S., and Chouaib, S. (2023). Tumor Microenvironment-Induced Tumor Cell Plasticity: Relationship with Hypoxic Stress and Impact on Tumor Resistance. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1222575"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yang, Y., Meng, W.-J., and Wang, Z.-Q. (2022). Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.803974"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12935-021-01840-z","article-title":"Clinical and Prognostic Significances of Cancer Stem Cell Markers in Gastric Cancer Patients: A Systematic Review and Meta-Analysis","volume":"21","author":"Razmi","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/s41556-021-00793-9","article-title":"A Tumour-Resident Lgr5+ Stem-Cell-like Pool Drives the Establishment and Progression of Advanced Gastric Cancers","volume":"23","author":"Fatehullah","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1158\/0008-5472.CAN-13-2309","article-title":"CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells","volume":"74","author":"Lau","year":"2014","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.stem.2009.11.013","article-title":"Lgr5(+ve) Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units in Vitro","volume":"6","author":"Barker","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21923","DOI":"10.1038\/srep21923","article-title":"Quantifying Lgr5-Positive Stem Cell Behaviour in the Pyloric Epithelium","volume":"6","author":"Leushacke","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/cr.2016.47","article-title":"Gastric Lgr5(+) Stem Cells Are the Cellular Origin of Invasive Intestinal-Type Gastric Cancer in Mice","volume":"26","author":"Li","year":"2016","journal-title":"Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Simon, E., Petke, D., B\u00f6ger, C., Behrens, H.-M., Warneke, V., Ebert, M., and R\u00f6cken, C. (2012). The Spatial Distribution of LGR5+ Cells Correlates with Gastric Cancer Progression. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035486"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1053\/j.gastro.2014.05.007","article-title":"Stem Cells Marked by the R-Spondin Receptor LGR5","volume":"147","author":"Koo","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jang, B.G., Lee, B.L., and Kim, W.H. (2013). Distribution of LGR5+ Cells and Associated Implications during the Early Stage of Gastric Tumorigenesis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082390"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8714","DOI":"10.3748\/wjg.v19.i46.8714","article-title":"Intestinal Stem Cell Marker LGR5 Expression during Gastric Carcinogenesis","volume":"19","author":"Zheng","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/stem.30","article-title":"Identification of Gastric Cancer Stem Cells Using the Cell Surface Marker CD44","volume":"27","author":"Takaishi","year":"2009","journal-title":"Stem Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ccr.2011.01.038","article-title":"CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System Xc(-) and Thereby Promotes Tumor Growth","volume":"19","author":"Ishimoto","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/bjc.2013.314","article-title":"CD44 Variant 9 Expression in Primary Early Gastric Cancer as a Predictive Marker for Recurrence","volume":"109","author":"Hirata","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4143\/crt.2014.227","article-title":"CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer","volume":"48","author":"Go","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/bjc.2016.401","article-title":"Prognostic Impact of CD44-Positive Cancer Stem-like Cells at the Invasive Front of Gastric Cancer","volume":"116","author":"Kodama","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s10120-021-01194-5","article-title":"Expression of CD44 Variant 9 Induces Chemoresistance of Gastric Cancer by Controlling Intracellular Reactive Oxygen Spices Accumulation","volume":"24","author":"Jogo","year":"2021","journal-title":"Gastric Cancer"},{"key":"ref_47","first-page":"5734549","article-title":"Aldehyde Dehydrogenase 1 in Gastric Cancer","volume":"2022","author":"Wang","year":"2022","journal-title":"J. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"P\u00e1dua, D., Barros, R., Amaral, A.L., Mesquita, P., Freire, A.F., Sousa, M., Maia, A.F., Caiado, I., Fernandes, H., and Pombinho, A. (2020). A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin. Cancers, 12.","DOI":"10.3390\/cancers12020495"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e30886","DOI":"10.1097\/MD.0000000000030886","article-title":"The Controversial Expression of SOX2 in Gastric Cancer and Its Correlation with Helicobacter Pylori Infection: A Meta-Analysis","volume":"101","author":"Li","year":"2022","journal-title":"Medicine"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhao, H., Hu, H., Chen, B., Xu, W., Zhao, J., Huang, C., Xing, Y., Lv, H., Nie, C., and Wang, J. (2021). Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.689139"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40246-016-0070-6","article-title":"The Clinical Significance of Snail Protein Expression in Gastric Cancer: A Meta-Analysis","volume":"10","author":"Chen","year":"2016","journal-title":"Hum. Genom."},{"key":"ref_52","first-page":"3845","article-title":"E-Cadherin Gene Mutations Provide Clues to Diffuse Type Gastric Carcinomas","volume":"54","author":"Becker","year":"1994","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1038\/sj.onc.1204234","article-title":"E-Cadherin Gene (CDH1) Promoter Methylation as the Second Hit in Sporadic Diffuse Gastric Carcinoma","volume":"20","author":"Machado","year":"2001","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/106689699800600302","article-title":"E-Cadherin Expression Is Correlated with the Isolated Cell\/Diffuse Histotype and with Features of Biological Aggressiveness of Gastric Carcinoma","volume":"6","author":"Machado","year":"1998","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1200\/JCO.2012.44.4612","article-title":"Somatic Mutations and Deletions of the E-Cadherin Gene Predict Poor Survival of Patients with Gastric Cancer","volume":"31","author":"Corso","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive Molecular Characterization of Gastric Adenocarcinoma. Nature, 513, 202\u2013209.","DOI":"10.1038\/nature13480"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s10120-021-01239-9","article-title":"Integrin \u03921 Orchestrates the Abnormal Cell-Matrix Attachment and Invasive Behaviour of E-Cadherin Dysfunctional Cells","volume":"25","author":"Figueiredo","year":"2022","journal-title":"Gastric Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0002-9440(10)64464-1","article-title":"Differential Expression of the Epithelial-Mesenchymal Transition Regulators Snail, SIP1, and Twist in Gastric Cancer","volume":"161","author":"Rosivatz","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00428-005-0118-9","article-title":"Expression and Nuclear Localization of Snail, an E-Cadherin Repressor, in Adenocarcinomas of the Upper Gastrointestinal Tract","volume":"448","author":"Rosivatz","year":"2006","journal-title":"Virchows Arch."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1111\/j.1349-7006.2012.02295.x","article-title":"Snail Is an Independent Prognostic Predictor for Progression and Patient Survival of Gastric Cancer","volume":"103","author":"He","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shin, N.R., Jeong, E.H., Choi, C.I., Moon, H.J., Kwon, C.H., Chu, I.S., Kim, G.H., Jeon, T.Y., Kim, D.H., and Lee, J.H. (2012). Overexpression of Snail Is Associated with Lymph Node Metastasis and Poor Prognosis in Patients with Gastric Cancer. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-521"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4103\/ijpm.ijpm_659_22","article-title":"The Clinical Significance of SNAIL, TWIST, and E-Cadherin Expression in Gastric Mesentery Tumor Deposits of Advanced Gastric Cancer","volume":"67","author":"Wu","year":"2024","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.12659\/MSM.912338","article-title":"Regulation of Proliferation and Epithelial-to-Mesenchymal Transition (EMT) of Gastric Cancer by ZEB1 via Modulating Wnt5a and Related Mechanisms","volume":"25","author":"Xue","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hou, W., Zhao, Y., and Zhu, H. (2023). Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015321"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e180013","DOI":"10.1001\/jamaoncol.2018.0013","article-title":"Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial","volume":"4","author":"Fuchs","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"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","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S1470-2045(23)00515-6","article-title":"Pembrolizumab plus Chemotherapy versus Placebo plus Chemotherapy for HER2-Negative Advanced Gastric Cancer (KEYNOTE-859): A Multicentre, Randomised, Double-Blind, Phase 3 Trial","volume":"24","author":"Rha","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1001\/jamaoncol.2020.3370","article-title":"Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-Line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial","volume":"6","author":"Shitara","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1001\/jamaoncol.2016.6762","article-title":"Mismatch Repair Deficiency, Microsatellite Instability, and Survival: An Exploratory Analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial","volume":"3","author":"Smyth","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1200\/JCO.19.01124","article-title":"Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer","volume":"37","author":"Pietrantonio","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.esmoop.2020.100036","article-title":"Predictive Role of Microsatellite Instability for PD-1 Blockade in Patients with Advanced Gastric Cancer: A Meta-Analysis of Randomized Clinical Trials","volume":"6","author":"Pietrantonio","year":"2021","journal-title":"ESMO Open"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s10120-021-01175-8","article-title":"Tumor Mutation Burden as a Biomarker in Resected Gastric Cancer via Its Association with Immune Infiltration and Hypoxia","volume":"24","author":"Wang","year":"2021","journal-title":"Gastric Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Satala, C.-B., Gur\u0103u, G., Patrichi, G., Gurau, A.-M., Mehedinti, R.-C., Leibovici, A.R., and Mihalache, D. (2026). FGFR2b in Gastric Cancer: Translating a Therapeutic Target into a Reliable Biomarker. Cancers, 18.","DOI":"10.3390\/cancers18121863"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/annonc\/mdi064","article-title":"Amplification of HER-2 in Gastric Carcinoma: Association with Topoisomerase II\u03b1 Gene Amplification, Intestinal Type, Poor Prognosis and Sensitivity to Trastuzumab","volume":"16","author":"Tanner","year":"2005","journal-title":"Ann. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in Combination with Chemotherapy versus Chemotherapy Alone for Treatment of HER2-Positive Advanced Gastric or Gastro-Oesophageal Junction Cancer (ToGA): A Phase 3, Open-Label, Randomised Controlled Trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1365-2559.2008.03028.x","article-title":"Assessment of a HER2 Scoring System for Gastric Cancer: Results from a Validation Study","volume":"52","author":"Hofmann","year":"2008","journal-title":"Histopathology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1200\/JCO.2015.62.6598","article-title":"Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013\/LOGiC\u2014A Randomized Phase III Trial","volume":"34","author":"Hecht","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1200\/JCO.2013.53.6136","article-title":"Lapatinib plus Paclitaxel versus Paclitaxel Alone in the Second-Line Treatment of HER2-Amplified Advanced Gastric Cancer in Asian Populations: TyTAN\u2014A Randomized, Phase III Study","volume":"32","author":"Satoh","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/S1470-2045(18)30481-9","article-title":"Pertuzumab plus Trastuzumab and Chemotherapy for HER2-Positive Metastatic Gastric or Gastro-Oesophageal Junction Cancer (JACOB): Final Analysis of a Double-Blind, Randomised, Placebo-Controlled Phase 3 Study","volume":"19","author":"Tabernero","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/S1470-2045(17)30111-0","article-title":"Trastuzumab Emtansine versus Taxane Use for Previously Treated HER2-Positive Locally Advanced or Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma (GATSBY): An International Randomised, Open-Label, Adaptive, Phase 2\/3 Study","volume":"18","author":"Shah","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1056\/NEJMoa2503119","article-title":"Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer","volume":"393","author":"Shitara","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1158\/0008-5472.CAN-07-5229","article-title":"FGFR2-Amplified Gastric Cancer Cell Lines Require FGFR2 and Erbb3 Signaling for Growth and Survival","volume":"68","author":"Kunii","year":"2008","journal-title":"Cancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/bjc.2011.603","article-title":"FGFR2 Gene Amplification and Clinicopathological Features in Gastric Cancer","volume":"106","author":"Matsumoto","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1158\/2159-8290.CD-15-1246","article-title":"High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial","volume":"6","author":"Pearson","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1200\/JCO.19.01834","article-title":"Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma","volume":"38","author":"Catenacci","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/S1470-2045(22)00603-9","article-title":"Bemarituzumab in Patients with FGFR2b-Selected Gastric or Gastro-Oesophageal Junction Adenocarcinoma (FIGHT): A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Study","volume":"23","author":"Wainberg","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s10120-024-01466-w","article-title":"Bemarituzumab as First-Line Treatment for Locally Advanced or Metastatic Gastric\/Gastroesophageal Junction Adenocarcinoma: Final Analysis of the Randomized Phase 2 FIGHT Trial","volume":"27","author":"Wainberg","year":"2024","journal-title":"Gastric Cancer"},{"key":"ref_88","unstructured":"Amgen (2026, August 09). A Randomized, Multi-Center, Double-Blind, Placebo-Controlled Phase 3 Study of Bemarituzumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Subjects with Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Satala, C.-B., Gurau, G., Gurau, A.-M., Patrichi, G., and Mihalache, D. (2026). Tumor Budding in Gastric Carcinoma: Beyond Counting Cells at the Invasive Front\u2014A Review of Current Evidence and Biological Perspectives. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27093787"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S1470-2045(13)70096-2","article-title":"Epirubicin, Oxaliplatin, and Capecitabine with or without Panitumumab for Patients with Previously Untreated Advanced Oesophagogastric Cancer (REAL3): A Randomised, Open-Label Phase 3 Trial","volume":"14","author":"Waddell","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S1470-2045(13)70102-5","article-title":"Capecitabine and Cisplatin with or without Cetuximab for Patients with Previously Untreated Advanced Gastric Cancer (EXPAND): A Randomised, Open-Label Phase 3 Trial","volume":"14","author":"Lordick","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pozzi, V., Campagna, R., Sartini, D., and Emanuelli, M. (2022). Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms. Biomolecules, 12.","DOI":"10.3390\/biom12091173"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nchembio.1204","article-title":"NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink","volume":"9","author":"Ulanovskaya","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41571-023-00852-0","article-title":"BRAF\u2014A Tumour-Agnostic Drug Target with Lineage-Specific Dependencies","volume":"21","author":"Hanrahan","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S1470-2045(22)00541-1","article-title":"Tumour-Agnostic Efficacy and Safety of Selpercatinib in Patients with RET Fusion-Positive Solid Tumours Other than Lung or Thyroid Tumours (LIBRETTO-001): A Phase 1\/2, Open-Label, Basket Trial","volume":"23","author":"Subbiah","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Dong, C., Wang, Y., Gu, X., Lv, X., Ren, S., Wang, Z., and Dai, Z. (2023). Differential diagnostic value of tumor markers and contrast-enhanced computed tomography in gastric hepatoid adenocarcinoma and gastric adenocarcinoma. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1222853"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"15353508241261473","DOI":"10.1177\/15353508241261473","article-title":"Comparison of Tumor Non-specific and PD-L1 Specific Imaging by Near-Infrared Fluorescence\/Cerenkov Luminescence Dual-Modality In-situ Imaging","volume":"23","author":"Zhang","year":"2024","journal-title":"Mol. Imaging"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:00:42Z","timestamp":1787662842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":98,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172757"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172757","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}