Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies

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Abstract
Aim: To investigate whether RhoA/ROCK pathway genes (RHOA, ROCK1, ROCK2) are differentially expressed in tunica albuginea of patients with congenital penile curvature (CPC) relative to Peyronie's disease (PD) and erectile dysfunction (ED), and to determine whether any differential expression is independent of clinical confounders. Material and Methods: This study enrolled 52 patients across three groups, as CPC (n=15), PD (n=15), and ED requiring penile prosthesis implantation (n=22). Tunica albuginea biopsies were obtained intraoperatively at standardised sites. RHOA, ROCK1, and ROCK2 mRNA levels were quantified by real-time qPCR using the 2-ΔΔCt method, normalised to GAPDH. Confounder adjustment was performed by multivariable linear regression and 1:2 nearestneighbour propensity score matching. Results: ROCK2 mRNA was elevated in CPC compared with PD (fold change, 1.28; 95% CI, 1.12-1.44; p=0.016) and ED (fold change, 1.21; 95% CI, 1.05-1.37; p=0.037). Neither RHOA nor ROCK1 differed significantly across groups. CPC group membership independently predicted higher ROCK2 in multivariable regression (β=0.189; 95% CI, 0.048-0.330; p=0.009) and in propensity score matched groups (mean difference, 0.21; 95% CI, 0.06-0.36; p=0.008). ROCK2 expression correlated positively with curvature severity (r=0.58; p=0.020). Conclusion: Selective ROCK2 upregulation distinguishes CPC from acquired penile conditions and is independent of age, BMI, and comorbidity burden. These findings suggest a developmental molecular mechanism distinct from fibrotic remodelling. Validation in larger multicentre cohorts with protein-level confirmation is required before clinical application.

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