{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:26:28Z","timestamp":1787199988912,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":230,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Cisplatin response in gastric cancer is shaped by malignant cell programs, stromal states, and mutation\u2010immune crosstalk, but the CAF subtypes linked to platinum tolerance and their epithelial effectors remain incompletely defined. We integrated single\u2010cell RNA sequencing, epithelial CNV\u2010like inference, fibroblast reclustering, CellChat analysis, signature scoring, hdWGCNA, CAF\u2010epithelial coupling, exploratory GSE14209 evaluation, TCGA\u2010STAD mutation\/copy\u2010number contextualization, and DepMap CRISPR virtual knockout analysis, followed by experimental validation in AGS and HGC\u201027 cells. IGF1+ CXCL12+ CAFs showed resistance\u2010supportive stromal features, and CAF\u2010epithelial coupling prioritized ARPC1A as a tumor epithelial candidate associated with this stromal program. In TCGA\u2010STAD, ARPC1A mutations were rare and consisted of three missense and two frameshift variants without a recurrent hotspot; the mutant tumors were confined to the MSI subtype and showed an immune\u2010activated, high TMB\/MSI context, indicating mutation\u2010immune crosstalk rather than a clear mutation\u2010specific CAF, EMT, drug resistance, or cisplatin response phenotype. By contrast, ARPC1A copy\u2010number gain\/amplification was more frequent and tracked with ARPC1A expression, CIN enrichment, aneuploidy, and fraction of genome altered. DepMap CRISPR data indicated mostly weak\u2010to\u2010mild baseline ARPC1A dependency in upper GI and gastric\/GEJ models. Experimentally, ARPC1A knockdown increased cisplatin sensitivity, promoted cisplatin\u2010induced apoptosis, and suppressed migration and invasion. These findings identify a CAF\u2010associated ARPC1A epithelial program linked to cisplatin response and support a mutation\u2010immune\/copy\u2010number framework in which ARPC1A is interpreted mainly through immune\u2010contextual mutation patterns and expression dosage rather than recurrent gain\u2010of\u2010function mutation.<\/jats:p>","DOI":"10.1155\/humu\/9607360","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:17:45Z","timestamp":1787199465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutation\u2010Immune Crosstalk Contextualizes CAF\u2010Associated ARPC1A Programs and Cisplatin Response in Gastric 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