ROCK2 Expression in Colorectal Cancer: Clinicopathological, Molecular, and Prognostic Associations

Background and Objectives: Rho-associated coiled-coil containing protein kinase 2 (ROCK2) regulates the actin cytoskeleton, cell migration, and proliferation, but its clinical relevance in colorectal cancer remains unclear. This study evaluated the clinicopathological, molecular, and prognostic associations of ROCK2 expression in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). Materials and Methods: RNA sequencing and clinical data from 439 COAD and 158 READ cases in The Cancer Genome Atlas (TCGA) were obtained through OncoLnc. Patients were classified into high- and low-ROCK2 expression groups using the median expression level. Clinicopathological associations, molecular correlations, survival outcomes, and Hallmark gene-set enrichment were analyzed. Prognostic associations were further evaluated in the independent GSE39582 colon cancer cohort. Results: In READ, high ROCK2 expression was more frequent in patients aged ≤65 years (p = 0.017), and its distribution differed by tumor site (p = 0.005). In COAD, high ROCK2 expression was less frequent in patients with a history of colon polyps (p = 0.013). ROCK2 expression was positively correlated with APC and KRAS expression in both COAD (R = 0.363 and 0.293, respectively; both p < 0.001) and READ (R = 0.543 and 0.282, respectively; both p < 0.001), and negatively correlated with TP53 expression in COAD only (R = −0.198, p < 0.001). High ROCK2 expression was associated with longer overall survival in COAD (p = 0.021) and READ (p = 0.045). In COAD, this association remained after multivariate adjustment (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.25–0.82, p = 0.009), although it was attenuated after multiple imputation of missing CEA values (p = 0.051). In GSEA, the mitotic spindle gene set was enriched in the high ROCK2 group, whereas oxidative phosphorylation, interferon response, and DNA repair gene sets were enriched in the low ROCK2 group in both cohorts. In GSE39582, the HR for high ROCK2 expression was below 1, but the primary multivariable analysis of overall survival did not reach statistical significance (HR = 0.80, p = 0.119), whereas high ROCK2 expression was associated with longer recurrence-free survival, a secondary endpoint (HR = 0.72, p = 0.032); this association was not reproduced with an alternative ROCK2 probe. Conclusions: ROCK2 expression was associated with key molecular features, including APC and KRAS expression, and with overall survival in TCGA COAD and READ. A similar prognostic direction was observed in an independent colon cancer cohort, although the primary overall survival analysis was not statistically significant. These prognostic associations warrant validation in additional cohorts and functional studies.