{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:30:42Z","timestamp":1788546642105,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ck0106890h0001"],"award-info":[{"award-number":["23ck0106890h0001"]}],"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":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Advanced gastric and gastroesophageal junction cancers (GC\/GEJCs) harbor diverse molecular signatures, highlighting the need for intricate evaluations to identify potential therapeutic targets. Although whole\u2010transcriptome sequencing (WTS) has emerged as a useful tool for understanding these molecular intricacies, its clinical implications have yet to be fully elucidated. This study evaluated the correlation between immunohistochemistry (IHC) and WTS, compared their clinical significance, and identified potential therapeutic targets undetectable through IHC alone. We enrolled 140 patients with advanced GC\/GEJC and assessed them using IHC for six pivotal biomarkers: claudin\u201018 (CLDN18), human epidermal growth factor receptor 2 (HER2), multiple receptor tyrosine kinases (RTKs), and programmed death ligand 1 (PD\u2010L1). Concurrently, WTS was employed as part of the analyses in MONSTAR\u2010SCREEN\u20102, a multicenter multiomics study. IHC analysis revealed 16.4% HER2, 39.3% CLDN18 (2+\/3\u2009+\u2009\u226575%), and 15.8% PD\u2010L1 (combined positive score\u2009\u2265\u200910) positivity, among other molecular markers. Significant correlations were observed between IHC and WTS for all six pivotal biomarkers. Among nineteen HER2 IHC\u2010positive patients treated with anti\u2010HER2 therapeutics, <jats:italic>ERBB2<\/jats:italic> status in WTS was significantly associated with progression\u2010free survival (<jats:italic>ERBB2<\/jats:italic>\u2010high vs. \u2010low: median 9.0 vs. 5.6\u2009months, log\u2010rank <jats:italic>p<\/jats:italic>\u2009=\u20090.046). IHC\u2010based molecular profiling revealed significantly high expression of CLDN18 in RTK\u2010negative patients, with 78.4% positive for either CLDN18 or PD\u2010L1. Additionally, WTS revealed elevated expression of pivotal biomarkers in patients displaying negative targetable biomarkers via IHC. Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of WTS. A subset with IHC\u2010negative but WTS\u2010positive status may benefit from specific biomarker\u2010targeted therapies.<\/jats:p>","DOI":"10.1111\/cas.16109","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T05:39:58Z","timestamp":1709357998000},"page":"1622-1633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Whole\u2010transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3759-1214","authenticated-orcid":false,"given":"Tadayoshi","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology National Cancer Center Hospital East  Kashiwa Japan"},{"name":"Translational Research Support Office National Cancer Center Hospital East  Kashiwa 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