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

Abstract

180 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). lncRNA Expression Pattern in PCa Altered in Metastatic Disease Direction (Metastatic vs Localized) Included in 12-lncRNA LSS Model PCA3 Upregulated No — Yes MALAT1 Upregulated Mild ↑ Yes SChLAP1 Upregulated Yes ↑ Yes HOTAIR Upregulated Yes ↑ Yes PCAT1 Upregulated Yes ↑ Yes PCGEM1 Upregulated No — Yes GAS5 Downregulated Yes ↓ Yes lincRNA-p21 Downregulated Yes ↓ Yes FR0348383 Upregulated Mild ↑ Yes FR348383 Upregulated Mild ↑ Yes UCA1 Upregulated Yes ↑ Yes NEAT1 Upregulated Yes ↑ Yes LINC01296 Upregulated Mild ↑ No TUG1 Upregulated Mild ↑ No MEG3 Downregulated Yes ↓ Yes SNHG16 Upregulated Mild ↑ No LINC00963 Upregulated Mild ↑ No LINC00161 Upregulated Mild ↑ No ANRIL Downregulated Yes ↓ Yes LINC00473 Upregulated Mild ↑ No