{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:55:44Z","timestamp":1790762144645,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Emerging evidence indicates that coagulation\u2010related molecular programs are associated with thrombosis, tumor progression, and molecular dysregulation in gastric cancer (GC). However, thrombosis\u2010associated molecular features in GC and their potential links to inherited susceptibility remain insufficiently understood. Integrated analyses of transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were performed to identify thrombosis\u2010associated genes and establish a machine learning\u2010based prognostic signature. Genome\u2010wide association study (GWAS), expression quantitative trait loci (eQTL), transcriptome\u2010wide association study (TWAS), and Mendelian randomization (MR) analyses were conducted to investigate susceptibility\u2010associated transcriptional programs in GC. Functional assays were used to evaluate candidate genes associated with malignant phenotypes. Single\u2010cell RNA sequencing (scRNA\u2010seq) and cell\u2013cell communication analyses were further performed to characterize cell\u2010type\u2010specific expression patterns and potential intercellular interactions. A total of 22 differentially expressed thrombosis\u2010associated genes were identified, and a prognostic signature comprising 14 genes was established. The signature stratified patients into high\u2010 and low\u2010risk groups and showed prognostic performance in both the training and validation cohorts. Integrative GWAS, eQTL, and TWAS analyses identified susceptibility\u2010associated transcriptional programs that were positively correlated with the thrombosis\u2010associated risk score. Silencing ACTN2 and CRYAB significantly reduced GC cell migration and invasion. scRNA\u2010seq analysis revealed relatively high CRYAB expression in neutrophils, and CellChat analysis suggested potential neutrophil\u2010B cell interactions involving COLLAGEN\u2010related signaling. This integrative multi\u2010omics study identified a thrombosis\u2010associated molecular signature linked to prognosis and germline susceptibility\u2010associated transcriptional programs in GC. ACTN2 and CRYAB may represent candidate genes associated with GC cell migration and invasion, while single\u2010cell analysis suggested potential immune\u2010related communication features.<\/jats:p>","DOI":"10.1111\/cbdd.70386","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:41:34Z","timestamp":1788327694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multi\u2010Omics Analysis Identifies Thrombosis\u2010Associated Molecular Features Linked to Germline Susceptibility and Immune Cell Communication in Gastric Cancer"],"prefix":"10.1111","volume":"108","author":[{"given":"Xiaogang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Emergency Xinqiao Hospital, Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Chongqing Southeast Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujun","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Oncology Chongqing Southeast Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Oncology Xinqiao Hospital, Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology Xinqiao Hospital, Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Oncology Xinqiao Hospital, Army Medical University  Chongqing 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