{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:48:24Z","timestamp":1785757704016,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007452","name":"WU JIEPING MEDICAL FOUNDATION","doi-asserted-by":"publisher","award":["320.6750.2025-06-271"],"award-info":[{"award-number":["320.6750.2025-06-271"]}],"id":[{"id":"10.13039\/100007452","id-type":"DOI","asserted-by":"publisher"}]},{"award":["320.6750.2025-06-271"],"award-info":[{"award-number":["320.6750.2025-06-271"]}],"id":[{"id":"https:\/\/ror.org\/05dgwj702","id-type":"ROR","asserted-by":"publisher"}]},{"name":"China Zhongguancun Precision Medicine Science and Technology Foundation","award":["GYLZH70"],"award-info":[{"award-number":["GYLZH70"]}]},{"name":"Suzhou Medical College of Soochow University\u2014Qilu Medical Research Fund","award":["24QL200107"],"award-info":[{"award-number":["24QL200107"]}]},{"name":"The Second Affiliated Hospital of Soochow University Scientific Research Pre-Research Fund","award":["SDFEYGZ2322"],"award-info":[{"award-number":["SDFEYGZ2322"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>This study aimed to characterize claudin 18.2 (CLDN18.2) expression in HER2-negative gastric or gastroesophageal junction cancer (GC\/GEJC) and to evaluate whether CLDN18.2 status is associated with clinicopathological features and outcomes after first line chemoimmunotherapy. We retrospectively analyzed 189 patients with HER2-negative GC\/GEJC treated at our institution from October 2019 to September 2024. CLDN18.2 expression was assessed by immunohistochemistry using two prespecified positivity thresholds: moderate to strong membranous staining (2+) in \u226540% or \u226575% of tumor cells. CLDN18.2 positivity was observed in 92\/189 patients (48.7%) using the \u226540% threshold and 69\/189 (36.5%) using the \u226575% threshold. PD L1 CPS \u2265 5 was less frequent in CLDN18.2 positive than in CLDN18.2 negative tumors at both thresholds (\u226540%: 8.7% vs. 23.7%, p = 0.003; \u226575%: 8.7% vs. 20.8%, p = 0.019). Among 87 patients receiving first line chemoimmunotherapy, CLDN18.2 status was not associated with significant differences in objective response rate, progression free survival, or overall survival. CLDN18.2 positive tumors showed lower PD L1 expression, but CLDN18.2 status did not identify a subgroup with differential benefit from first line chemoimmunotherapy. These findings suggest that CLDN18.2 status does not appear to serve as a predictive biomarker for immune checkpoint inhibitor-based treatment.<\/jats:p>","DOI":"10.3390\/curroncol33080460","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Claudin 18.2 Expression and Outcomes of First-Line Chemoimmunotherapy in HER2-Negative Gastric or Gastroesophageal Junction Cancer: A Single-Center Retrospective Study"],"prefix":"10.3390","volume":"33","author":[{"given":"Run","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hangzhou First People\u2019s Hospital Tonglu Campus, Hangzhou 311500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Zhangjiagang First People\u2019s Hospital, Suzhou 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaofeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chronic Non-Communicable Diseases, Suzhou Center for Disease Control and Prevention, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chronic Non-Communicable Diseases, Suzhou Center for Disease Control and Prevention, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-1129","authenticated-orcid":false,"given":"Wangyang","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","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_3","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_4","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_5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/s41571-024-00874-2","article-title":"Claudin 18.2 as a novel therapeutic target","volume":"21","author":"Nakayama","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17588359251344804","DOI":"10.1177\/17588359251344804","article-title":"Emerging evidence of targeting non-oncogenic drivers for gastric cancer: Claudin18.2 and beyond","volume":"17","author":"Yamamoto","year":"2025","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_7","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_8","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_9","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_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S1470-2045(24)00636-3","article-title":"Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): A multicentre, open-label, single-arm, phase 1 trial","volume":"26","author":"Ruan","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1038\/s41591-025-03783-8","article-title":"CLDN18.2-targeting antibody-drug conjugate IBI343 in advanced gastric or gastroesophageal junction adenocarcinoma: A phase 1 trial","volume":"31","author":"Liu","year":"2025","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1016\/S0140-6736(25)00860-8","article-title":"Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician\u2019s choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): A randomised, open-label, phase 2 trial","volume":"405","author":"Qi","year":"2025","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100261","DOI":"10.1016\/j.esmogo.2025.100261","article-title":"Distinct clinicopathological and survival profiles of CLDN18.2 and PD-L1 expression in advanced gastric cancer and gastroesophageal junction adenocarcinoma","volume":"10","author":"Castillo","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e012683","DOI":"10.1136\/jitc-2025-012683","article-title":"Dynamic modulation of claudin18.2 expression and remodeling of the tumor microenvironment in gastric cancer during chemo-immunotherapy","volume":"13","author":"Lim","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1186\/s12967-026-08408-3","article-title":"Claudin18.2 and the PD-1\/PD-L1 axis in gastric cancer: Mechanistic insights and implications for combination immunotherapy","volume":"24","author":"Lu","year":"2026","journal-title":"J. Transl. Med."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"78","DOI":"10.21147\/j.issn.1000-9604.2024.01.08","article-title":"Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer: A retrospective study","volume":"36","author":"Qi","year":"2024","journal-title":"Chin. J. Cancer Res."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","unstructured":"Jia, K., Chen, Y., Sun, Y., Hu, Y., Jiao, L., Ma, J., Yuan, J., Qi, C., Li, Y., and Gong, J. (2022). Multiplex immunohistochemistry defines the tumor immune microenvironment and immunotherapeutic outcome in CLDN18.2-positive gastric cancer. BMC Med., 20.","DOI":"10.1186\/s12916-022-02421-1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s10120-024-01566-7","article-title":"Survival outcomes of patients with gastric cancer treated with first-line nivolumab plus chemotherapy based on claudin 18.2 expression","volume":"28","author":"Kim","year":"2025","journal-title":"Gastric Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Miyajima, Y., and Kawakami, T. (2025). Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1. Cancers, 17.","DOI":"10.3390\/cancers17071120"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/PAI.0000000000001248","article-title":"Claudin 18.2 Immunohistochemistry Expression in Gastric Cancer: A Systematic Review","volume":"33","author":"Iglesias","year":"2025","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100210","DOI":"10.1016\/j.esmogo.2025.100210","article-title":"The prognostic role of Claudin 18.2 in advanced gastric or gastroesophageal junction adenocarcinoma: A systematic literature review","volume":"9","author":"Fassan","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/jjco\/hyz068","article-title":"Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma","volume":"49","author":"Rohde","year":"2019","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.4251\/wjgo.v15.i2.343","article-title":"Prognostic value of claudin 18.2 expression in gastric adenocarcinoma","volume":"15","author":"Kayikcioglu","year":"2023","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1007\/s12094-020-02380-0","article-title":"Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas","volume":"22","author":"Arnold","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.21037\/tcr-19-1876","article-title":"Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer","volume":"9","author":"Hong","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"2413913","DOI":"10.1002\/advs.202413913","article-title":"A CLDN18.2-Targeted Nanoplatform Manipulates Magnetic Hyperthermia Spatiotemporally for Synergistic Immunotherapy in Gastric Cancer","volume":"12","author":"Wang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41416-019-0508-4","article-title":"Claudin-18 expression in oesophagogastric adenocarcinomas: A tissue microarray study of 523 molecularly profiled cases","volume":"121","author":"Coati","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1001\/jama.2023.19918","article-title":"Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial","volume":"330","author":"Xu","year":"2023","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1200\/JCO.21.01862","article-title":"Low Programmed Death-Ligand 1-Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma","volume":"40","author":"Zhao","year":"2022","journal-title":"J. Clin. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/8\/460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:23:59Z","timestamp":1785756239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/8\/460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["curroncol33080460"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33080460","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}