A non-invasive lncRNA biomarker model for detection and metastatic risk prediction in prostate cancer.

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Background: Early detection and precise metastatic risk stratification in prostate cancer (PCa) remain major challenges. PSA-based screening lacks specificity, often delaying identification of aggressive disease. Long non-coding RNAs (lncRNAs) are promising minimally invasive biomarkers due to stability in circulation and tumor-specific dysregulation. Methods: We profiled circulating and urinary levels of 20 lncRNAs—PCA3, MALAT1, SChLAP1, HOTAIR, PCAT1, PCGEM1, GAS5, lincRNA-p21, FR0348383, FR348383, UCA1, NEAT1, LINC01296, TUG1, MEG3, SNHG16, LINC00963, LINC00161, ANRIL, LINC00473—in 400 men (200 biopsy-confirmed PCa, 200 controls) using standardized qRT-PCR workflows. Differential expression analysis identified lncRNA signatures associated with tumor initiation and metastatic progression. Results: Metastatic cases exhibited upregulation of SChLAP1, HOTAIR, PCAT1, UCA1, and NEAT1 and downregulation of GAS5, lincRNA-p21, MEG3, and ANRIL. A logistic regression–based composite model incorporating the top 12 discriminative lncRNAs yielded high diagnostic accuracy (cancer vs. control AUC: 0.94; localized vs. metastatic AUC: 0.91). We derived a lncRNA-based severity score (LSS) to predict disease aggressiveness: LSS=i=1∑12 (βi ×lncRNAi) where βi represents the regression coefficient for each lncRNA and lncRNAi its normalized expression. Higher LSS values correlated with metastatic disease, elevated Gleason scores, and PSA levels (p < 0.001). Integration with paired tumor mRNA validated the biological relevance of LSS, linking it to chromatin remodeling, EMT, androgen receptor signaling, and metastatic pathways. Conclusions: This 20-lncRNA liquid biopsy panel with a severity score provides a non-invasive, clinically actionable framework for early detection, metastatic risk prediction, and precision management in PCa. The findings support prospective validation and integration into clinical decision-making for stratified patient care.

Differential expression of 20 circulating and urinary lncRNAs in prostate cancer and their contribution to the LncRNA severity score (LSS).