Abstract / Summary
Abstract Prostate cancer (PCa) remains one of the leading causes of cancer-related morbidity and mortality among men worldwide, largely due to limitations in early detection and reliable stratification of aggressive disease. Although serum prostate-specific antigen (PSA) is widely used for screening, its limited specificity necessitates the identification of more robust non-invasive biomarkers. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis and metastasis and hold promise as circulating biomarkers.The present study aimed to evaluate the diagnostic and prognostic potential of selected circulating lncRNAs (HOTAIR, MALAT1, SCHLAP1, PCAT, GAS5, FR0348383, and lincRNA-p21) in prostate cancer. Quantitative expression profiling was performed, followed by receiver operating characteristic (ROC) analysis to assess discriminatory performance relative to PSA and Gleason score. In parallel, integrative bioinformatics analyses including protein–protein interaction (PPI) networking, Gene Ontology enrichment, and pathway mapping were conducted to elucidate underlying molecular mechanisms. Our findings demonstrate significant upregulation of HOTAIR, MALAT1, SCHLAP1, PCAT, and lincRNA-p21 in metastatic disease, with MALAT1 and SCHLAP1 showing superior diagnostic accuracy (AUC up to ~ 0.98) compared with PSA. Network analysis revealed central oncogenic hubs including MTOR, AKT1, TP53, EGFR, and MYC, highlighting coordinated regulation of epigenetic remodeling, metabolic reprogramming, and proliferative signaling. Functional enrichment further indicated strong involvement of hypoxia response, EMT, and Wnt signaling pathways. Collectively, this study supports circulating lncRNAs as powerful non-invasive biomarkers for prostate cancer stratification and provides mechanistic insight into the integrated oncogenic–metabolic network driving disease progression. These findings may facilitate improved risk assessment and precision management of prostate cancer.