Plasma urotensin-2 levels as a potential biomarker in prostate cancer: Analysis across disease stages

Prostate cancer (PCa) remains a leading cause of cancer-related mortality among men. Although prostate-specific antigen (PSA) is a key biomarker, its diagnostic and prognostic limitations necessitate the identification of novel markers. Urotensin-2 (UT-2), a potent vasoactive peptide, has been implicated in the pathogenesis of several malignancies, but its role in prostate cancer remains underexplored. This study aimed to evaluate plasma UT-2 levels across disease stages in PCa and assess its potential as a biomarker for metastatic disease. This cross-sectional study included 147 male patients: 100 with metastatic PCa and 47 controls (comprising benign prostatic hyperplasia [BPH], localized, and locally advanced PCa). Plasma UT-2 levels were quantified using ELISA. Statistical analyses included analysis of variance, Kruskal-Wallis, and receiver operating characteristic (ROC) curve analysis to assess UT-2's discriminative ability and its correlation with clinical parameters such as Gleason score, ISUP grade, and PSA. UT-2 levels were significantly elevated in metastatic PCa patients (mean: 2.03 ± 0.91 ng/mL) compared to control groups (BPH: 1.42 ± 0.61 ng/mL; localized: 1.46 ± 0.71 ng/mL; locally advanced: 1.41 ± 0.76 ng/mL; P = .002). ROC analysis demonstrated a moderate discriminatory ability for metastasis (AUC = 0.70, 95% CI: 0.61-0.79), with a cutoff of 1.269 ng/mL yielding 81% sensitivity and 53% specificity. No significant associations were observed between UT-2 levels and Gleason score, ISUP grade, PSA levels, or metastatic site. This is the first clinical study to evaluate plasma UT-2 levels in PCa patients. Elevated UT-2 levels in metastatic cases, independent of traditional prognostic markers, suggest its potential utility in identifying systemic disease burden. While not suitable as a standalone diagnostic tool, UT-2 may serve as a complementary biomarker within a multiparameter panel to improve prognostication and risk stratification in PCa. Further prospective and longitudinal studies are warranted to validate its prognostic significance.