{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:06:14Z","timestamp":1792058774937,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":123,"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>Translating high\u2010resolution multiomics data into clinically actionable biomarkers is critical for overcoming therapeutic resistance and tumor heterogeneity in prostate adenocarcinoma (PRAD). To decode the complex immunosuppressive tumor microenvironment (TME) and identify robust prognostic targets, we developed a systematic biomarker discovery pipeline integrating single\u2010cell RNA sequencing (scRNA\u2010seq) mapping and high\u2010dimensional network analysis. By deconvoluting scRNA\u2010seq profiles from over 35,000 PRAD cells, nonnegative matrix factorization (NMF) of the malignant epithelial compartment revealed nine distinct transcriptional metaprograms (MPs). High\u2010dimensional weighted gene coexpression network analysis (hdWGCNA) pinpointed PRAD\u2010MP7 as the core proliferative engine and nominated the malignant\u2010specific gene YBX1 as the master prognostic hub. To establish clinical utility evidence, we validated YBX1 across six independent global PRAD cohorts, where its overexpression robustly predicted poor overall survival (OS) and relapse\u2010free survival (RFS). In vitro functional validation via siRNA\u2010mediated knockdown in DU\u2010145 and PC\u20103 cells significantly attenuated proliferative and invasive capacities, impairing cell viability and downregulating key progression markers (Ki\u201067, MMP2, and MMP9). Crucially, immunogenomic profiling mapped YBX1 expression to an \u201cimmune\u2010excluded\u201d TME, characterized by depleted CD8+ T cell and dendritic cell infiltration alongside elevated immune checkpoint networks. Serving as a bridge to clinical translation, YBX1 effectively predicted clinical responses in three immunotherapy cohorts and demonstrated broad resistance to 12 chemotherapeutic and targeted agents. Our multiomics integration pipeline highlights YBX1 as a dual\u2010functional oncogene that couples malignant proliferation with immune evasion, establishing it as a highly translational biomarker and an actionable target for precision PRAD management.<\/jats:p>","DOI":"10.1155\/humu\/2147624","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:25:23Z","timestamp":1777879523000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Single\u2010Cell Multiomics Pipeline Maps YBX1 as a Functional Biomarker for Immune Evasion and Therapeutic Resistance in Prostate 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