LncRNA expression in prostate cancer: From in silico analysis to urinary EV-based liquid biopsy for prognosis

Prostate cancer (PCa) is the most frequently diagnosed malignancy among men and remains a leading cause of cancer-related death. Despite the widespread use of diagnostic tools such as PSA testing and Gleason scoring, these methods often fall short in accurately predicting tumor progression, highlighting the urgent need for reliable, non-invasive biomarkers to improve prognosis. In this study, we explored the potential of long non-coding RNAs (lncRNAs) as novel prognostic biomarkers for PCa. An initial in silico analysis of public datasets identified six lncRNAs differentially expressed in PCa tissues compared to healthy and adjacent non-tumor tissues. Of these, three were validated in a cohort of prostate cancer and benign prostatic hyperplasia (BPH) tissue samples. Notably, four lncRNAs showed expression levels that increased with higher Gleason scores, suggesting their potential as indicators of disease progression rather than early detection. To evaluate their applicability in a non-invasive setting, we assessed the expression of these lncRNAs in urinary extracellular vesicles (EVs). The results evidenced that Lnc-OPRK1-3 and lnc-SRSF6-1 are candidates as non-invasive prognostic biomarkers since they were detectable in urine and exhibited expression levels that correlate with advancing disease, specifically in the transition from Gleason score 3 + 3 to 4 + 3 and above. Their detection through urine-based liquid biopsy could support more precise patient stratification and suggest clinical decision-making. Further investigation is needed to validate their functional relevance and clinical utility.