Background: Cuproptosis, along with RNA methylation regulators, has recently come to the fore as innovative mechanisms governing cell death, exerting profound impact on the onset and progression of multiple cancers. Nonetheless, the prognostic implications and underlying regulatory mechanisms of them associated with prostate cancer (PCa) remain to be thoroughly investigated.Methods: Genomic and clinical data for PCa from The Cancer Genome Atlas datasets were analyzed to identify a prognostic model through univariate and Least Absolute Shrinkage and Selection Operator Cox regression analyses that were validated utilizing external datasets. We used receiver operating characteristic curves and C-index to evaluate the accuracy of our prognostic model. In conjunction with this, we conducted single-cell RNA sequencing (scRNA-seq) analyses to investigate underlying mechanisms and evaluate the degree of immune infiltration, as well as to assess patients’ responses to diverse chemotherapy agents. Especially, qPCR assay was utilized to unveil the expression of signature genes in PCa.Results: We meticulously selected six Cuproptosis-Associated RNA Methylation Regulators (CARMRs) to establish a risk prognosis model, which was further verified to obtain enhanced predictive capacity in external validation cohorts. Insights from immune infiltration and scRNA-seq analyses have elucidated the immune characteristics of PCa, and highlighted the immunosuppressive role of regulatory T cells on immune response. Additionally, drug susceptibility analysis demonstrated that patients with PCa in the low-risk category derived better benefit from bicalutamide treatment, whereas those in the high-risk group exhibited a favor response to adriamycin and docetaxel treatments. The qPCR and immunohistochemistry (IHC) staining assays also reveal the a dramatically altered expression pattern of TRDMT1 and ALYREF in PCa tissues.Conclusion: In general, we established a model involving CARMRs that can better predict the risk of recurrence of PCa and have identified the possible mechanisms affecting PCa progression, thereby promoting further research in this field.

Prostate cancer (PCa) is an extremely heterogeneous cancer and is highly prevalent in the older male population. Since intra‐tumour 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‐cell RNA sequencing data extracted from PCa and CRPC samples were analysed via sub‐clustering, 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‐gene signature underlying a prostate cancer meta‐program (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–cell communication analyses, we illustrated that PCMP genes exert oncogenic effects by enhancing the proliferation and oxidative phosphorylation of epithelial cells. Intra‐cellular 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.

Background: As a highly prevalent tumor in males, prostate cancer (PCa) needs newly developed biomarkers to guide prognosis and treatment. However, few researches have elaborated on the function of cuproptosis-associated RNA methylation regulators (CARMRs).