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Here, using a training cohort of 107 newly diagnosed prostate cancer patients, primary staged by\n                    <jats:sup>68<\/jats:sup>\n                    Gallium prostate\u2010specific membrane antigen (PSMA) Positron Emission Tomography\u2010Computed Tomography (PET\/CT) imaging (41 localized and 66 metastatic; Cohort 1), we aimed to train a gene expression signature associated with metastasis, a key hallmark of aggressiveness. By mRNA sequencing of primary tumor tissue samples from 107 patients in Cohort 1 and use of Least Absolute Shrinkage and Selection Operator regression, we trained a novel 14\u2010gene model (CaP14) that distinguished localized and metastatic prostate cancer (MPC). Associations between CaP14 and disease outcomes were tested in three independent cohorts, including 17 MPC and 127 radical prostatectomy (RP) patients (Cohort 2), 473 RP patients (Cohort 3), and 174 RP patients (Cohort 4), respectively. Diagnostic\/prognostic performance of CaP14 was assessed by receiver operating characteristics, Kaplan\u2013Meier, uni\/multivariate Cox regression, and biochemical recurrence (BCR)\u2010free and prostate cancer\u2010specific survival analyses. A high CaP14 score was associated with metastasis and poor prostate cancer\u2010specific survival in Cohorts 1 and 2, and with early BCR in RP Cohorts 2, 3, and 4 independently of routine clinical variables. This is the first study to develop a gene signature capable of predicting metastasis at initial diagnosis, trained using a cohort of patients whose metastatic spread was evaluated using\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010PSMA PET\/CT scans. CaP14 has the potential to guide better and more personalized treatment decisions for newly diagnosed prostate cancer in the future.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70247","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:57:37Z","timestamp":1763377057000},"page":"1406-1419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Training and validation of a novel 14\u2010gene expression signature associated with prostate cancer metastasis and postoperative recurrence"],"prefix":"10.1002","volume":"158","author":[{"given":"Eva F.","family":"Jensby","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine Aarhus University Hospital (AUH)  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus 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