{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:11:32Z","timestamp":1791483092820,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["AMED: 24ck0106890h0002"],"award-info":[{"award-number":["AMED: 24ck0106890h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Claudin 18.2 (CLDN18.2), a tight junction protein isoform, is an emerging therapeutic target in oncology. CLDN18 is well\u2010characterized in gastric cancer, but its pan\u2010cancer expression profiles and isoform distributions are poorly documented. In the present study, we analyzed CLDN18 expression in patients with solid tumors enrolled in the MONSTAR\u2010SCREEN\u20102 study using immunohistochemistry (IHC, <jats:italic>n<\/jats:italic>\u2009=\u2009349) and whole\u2010transcriptome sequencing (WTS, <jats:italic>n<\/jats:italic>\u2009=\u20092191). A splice junction analysis algorithm characterized isoform distribution patterns in WTS data and evaluated temporal changes using paired pre\u2010 and postchemotherapy specimens. IHC detected CLDN18.2 (\u2265\u200940% of tumor cells showing any staining intensity) in 16.3% of patients, with highest prevalence in gastric (54.5%), biliary tract (21.7%), pancreatic (20.7%), and small intestinal (18.2%) cancers. WTS and IHC findings were significantly correlated (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). WTS analysis with optimized transcript thresholds (<jats:italic>n<\/jats:italic>\u2009=\u20092191) demonstrated the <jats:italic>CLDN18<\/jats:italic>\u2010high population to be 13.8%, with highest proportions in gastric (64.5%), small intestinal (40.0%), pancreatic (37.8%), and biliary tract (20.0%) cancers. Isoform analysis of 364 patients revealed <jats:italic>CLDN18.2<\/jats:italic> predominance (mean 18.2\/18.1 proportion 0.945), with <jats:italic>CLDN18.1<\/jats:italic> predominance observed in only 4.9% of patients. Longitudinal analysis of 27 paired gastric cancer samples revealed a significant reduction in <jats:italic>CLDN18<\/jats:italic> expression and a nonsignificant decrease in the <jats:italic>CLDN18.2<\/jats:italic> proportion following chemotherapy. This analysis validates WTS as a complementary approach to IHC for CLDN18 assessment and demonstrates significant <jats:italic>CLDN18<\/jats:italic> expression across multiple cancer types. The predominance of <jats:italic>CLDN18.2<\/jats:italic> supports the expansion of targeted therapeutic approaches beyond gastric cancer and indicates the potential of RNA\u2010based screening.<\/jats:p>","DOI":"10.1111\/cas.70100","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:39:30Z","timestamp":1748867970000},"page":"2218-2231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Landscape Analysis of <scp><i>CLDN18<\/i><\/scp> Expression and Isoform Distribution in Solid Tumors: Insights From <scp>MONSTAR<\/scp>\u2010<scp>SCREEN<\/scp>\u20102 Study"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3759-1214","authenticated-orcid":false,"given":"Tadayoshi","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Translational Research Support Office National Cancer Center Hospital East  Kashiwa Japan"},{"name":"Department of 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