{"entity": "publication", "iuid": "cc5365ff98814141a42cbc2c55c1b6ff", "timestamp": "2026-09-17T19:11:33.849Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cc5365ff98814141a42cbc2c55c1b6ff.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cc5365ff98814141a42cbc2c55c1b6ff"}}, "title": "A novel multiomics machine learning signature identifies rapid progression in clinically low risk prostate cancer.", "authors": [{"family": "Rafeletou", "given": "Alexandra", "initials": "A"}, {"family": "Fathi", "given": "Faezeh", "initials": "F"}, {"family": "Kise\u013cova", "given": "Tatjana", "initials": "T"}, {"family": "Taheri", "given": "Golnaz", "initials": "G", "orcid": "0000-0002-2741-0355", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/014c217121d346b2b371bbc1c2fede57.json"}}, {"family": "Lundberg", "given": "Arian", "initials": "A", "orcid": "0000-0002-6630-2787", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/baa2c7c8963840bfb6a22d7c5cfe35f9.json"}}], "type": "journal article", "published": "2026-09-14", "journal": {"title": "NPJ Digit Med", "issn": "2398-6352", "issn-l": null, "volume": "9", "issue": "1", "pages": null}, "abstract": "Risk stratification in primary prostate cancer remains heavily reliant on clinicopathological criteria that frequently miss the heterogeneity underlying early aggressive disease. We present a novel machine learning non-linear prognostic framework encoding somatic copy-number alterations and biological information associated with gene products, along with an integrative multi-omics approach including epigenomics and transcriptomics into a patient-specific biological network. Applied to the TCGA-PRAD (n = 498), our weighted graph-based feature selection and LASSO-Cox model identified ZNF268 as a master regulator gene, in which the hypermethylation of its promoter region is linked to a distinct oncogenic transition exclusive to Low/Intermediate-risk disease. Post-hoc analysis of Low-ZNF268 tumors showed a distinct somatic landscape enriched for driver mutations and predicted sensitivity to MAPK, ATR, and PI3K/mTOR inhibitors, providing potential therapeutic vulnerabilities alongside the prognostic signal. Topological network analysis further revealed that ZNF268 loss impacts a co-expression rewiring gene network, quantified as a Rewiring Score: associated with Progression-Free Survival in the TCGA-PRAD (HR: 2.79, 95% CI: 1.36-5.71, p = 0.0049) and Biochemical Recurrence in two external cohorts. By capturing tumors at an active molecular transition state preceding systemic progression, this framework offers a prognostic tool to identify biologically aggressive prostate cancer disease within patients currently undertreated by standard risk criteria.", "doi": "10.1038/s41746-026-03254-5", "pmid": "42736338", "labels": {"Arian Lundberg": null, "DDLS Fellow": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41746-026-03254-5"}, {"db": "pmc", "key": "PMC13575102"}], "notes": [], "created": "2026-09-17T08:55:54.574Z", "modified": "2026-09-17T08:58:40.601Z"}