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Since intra\u2010tumour heterogeneity (ITH) commonly results in PCa chemotherapy resistance and recurrence, it is critical to explore its effects on tumour behaviour. Prognostic genes related to ITH were identified, and a signature was constructed using Cox regression analyses and multiple machine learning algorithms. Single\u2010cell RNA sequencing data extracted from PCa and CRPC samples were analysed via sub\u2010clustering, pseudotime, cell communication and drug sensitivity approaches to elucidate their function. The oncogenic potential of hub genes was confirmed by immunohistochemistry and cell proliferation assays. An 11\u2010gene signature underlying a prostate cancer meta\u2010program (PCMP) was generated by selecting an optimal combination of machine learning methods. Survival assays and multivariate Cox regression analyses conducted in multiple cohorts revealed the superior prognostic value of the PCMP signature. Functional enrichment analyses indicated that it dysregulates the cell cycle. Using trajectory and cell\u2013cell communication analyses, we illustrated that PCMP genes exert oncogenic effects by enhancing the proliferation and oxidative phosphorylation of epithelial cells. Intra\u2010cellular assays also demonstrated that CENPA and CKS1B had promising malignant potential. In summary, our research not only establishes the association between the PCMP signature and reveals its malignant characteristics, but also deepens our understanding of the mechanisms underlying PCa progression and ITH. It holds promise for the development of targeted therapeutic interventions, thereby offering clinical benefits to patients.<\/jats:p>","DOI":"10.1111\/jcmm.70806","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:20:54Z","timestamp":1756218054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single\u2010Cell and Bulk <scp>RNA<\/scp> Sequencing Highlights Intra\u2010Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer"],"prefix":"10.1111","volume":"29","author":[{"given":"Junchao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Institute of Urology Anhui Medical University  Hefei China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation Anhui Medical University  Hefei 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