Multi-omics approach for identifying CNV-associated lncRNA signatures with prognostic value in prostate cancer

Background: Prostate cancer, the second most prevalent malignancy among men, poses a significant threat to affected patients' well-being due to its poor prognosis. Novel biomarkers are required to enhance clinical out-comes and tailor personalized treatments. Herein, we describe our research to explore the prognostic value of long non-coding RNAs (lncRNAs) deregulated by copy number variations (CNVs) in prostate cancer. Methods: The study employed an integrative multi-omics data analysis of the prostate cancer transcriptomic, CNV and methylation datasets to identify prognosis-related subtypes. Subtype-specific expression profiles of protein -coding genes (PCGs) and lncRNAs were determined. We analysed CNV patterns of lncRNAs across the genome to identify subtype-specific lncRNAs with CNV changes. LncRNAs exhibiting significant amplification or deletion and a positive correlation were designated CNV-deregulated lncRNAs. A prognostic risk score model was sub-sequently developed using these CNV-driven lncRNAs. Results: Six molecular subtypes of prostate cancer were identified, demonstrating significant differences in prognosis (P = 0.034). The CNV profiles of subtype-specific lncRNAs were examined, revealing their correlation with CNV amplification or deletion. Six lncRNAs (CCAT2, LINC01593, LINC00276, GACAT2, LINC00457, LINC01343) were selected based on significant CNV amplifications or deletions using a rigorous univariate Cox proportional risk regression model. A robust risk score model was developed, stratifying patients into high-risk and low-risk categories. Notably, our prognostic model based on these six lncRNAs exhibited exceptional pre-dictive capabilities for recurrence-free survival (RFS) in prostate cancer patients (P = 0.024). Conclusions: Our study successfully identified a prognostic risk score model comprising six CNV-driven lncRNAs that could potentially be prognostic biomarkers for prostate cancer. These lncRNA signatures are closely associated with RFS, providing promising prospects for improved patient prognostication and personalized therapeutic strategies for novel prostate cancer treatment.