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Current clinicopathological factors inadequately predict biochemical recurrence, a critical indicator guiding post\u2010treatment strategies following radical prostatectomy. To address this, we conducted a meta\u2010analysis of four large\u2010scale PCa datasets and found 33 previously reported PCa\u2010associated genes to be consistently up\u2010regulated in prostate tumours. By analysing single\u2010cell RNA\u2010sequencing data, we found these genes predominantly as markers in epithelial cells. Subsequently, we applied 97 advanced machine\u2010learning algorithms across five PCa cohorts and developed an 11\u2010gene epithelial expression signature. This signature robustly predicted biochemical recurrence\u2010free survival (BCRFS) and stratified patients into distinct risk categories, with high\u2010risk patients showing worse survival and altered immune cell populations. The signature outperformed traditional clinical parameters in larger cohorts and was overall superior to published PCa signatures for BCRFS. By analysing peripheral blood data, four of our signature genes showed potential as biomarkers for radiation response in patients with localised cancer and effectively stratified castration\u2010resistant patients for overall survival. In conclusion, this study developed a novel epithelial gene\u2010expression signature that enhanced BCRFS prediction and enabled effective risk stratification compared to existing clinical\u2010 and gene\u2010expression\u2010derived prognostic tools. Furthermore, a set of genes from the signature demonstrated potential utility in peripheral blood, a tissue amenable to minimally invasive sampling in a primary care setting, offering significant prognostic value for PCa patients without requiring a tumour biopsy.<\/jats:p>","DOI":"10.1002\/1878-0261.13804","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T01:45:46Z","timestamp":1740015946000},"page":"1811-1835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integration of single\u2010cell and bulk\n                    <scp>RNA<\/scp>\n                    \u2010sequencing data reveals the prognostic potential of epithelial gene markers for prostate cancer"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9993-149X","authenticated-orcid":false,"given":"Zhuofan","family":"Mou","sequence":"first","affiliation":[{"name":"Department of Clinical 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