Prognostic Significance of Cdc42 Expression in Colorectal Cancer and Its Concordance Between Primary Tumors and Matched Metastases: A Retrospective Observational Study.

Background and Objectives: Aberrant activation or overexpression of cell division cycle 42 (Cdc42) has been demonstrated in various tumors; however, its prognostic relevance in colorectal cancer (CRC) remains insufficiently defined. Thus, we evaluated the prognostic impact of Cdc42 expression in patients with CRC. In a paired primary-metastasis subset, we also assessed the concordance of Cdc42 expression between primary tumors and matched metastatic tissues. Materials and Methods: Cdc42 expression was assessed by immunohistochemistry in patients with colorectal cancer who underwent colectomy for curative or palliative purposes between January 2009 and January 2019. Cdc42 expression was quantified as a staining index and then dichotomized into low- and high-Cdc42 groups using a median cutoff value of six. Overall survival (OS) was analyzed by Kaplan-Meier curves with log-rank testing, and independent prognostic factors were assessed using Cox proportional hazard models. Results: The study included 94 patients (median age, 60 years) with a median follow-up of 88.4 months. High Cdc42 expression was significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type status (p = 0.001), lymph node metastasis (p = 0.039), and perineural invasion (p = 0.021). Patients with high Cdc42 expression had significantly poorer OS than those with low expression (median OS: 48.5 months, 95% confidence interval [CI]: 33.3-63.7 vs. 114.4 months, 95% CI: 24.0-204.9; p = 0.003). In multivariable Cox regression, high Cdc42 expression remained an independent predictor of worse OS (hazard ratio [HR]: 2.365, 95% CI: 1.336-4.184; p = 0.003), together with advanced stage and moderate-to-poor differentiation. In the paired primary-metastasis subset, Cdc42 expression in primary tumors correlated positively with that in matched metastases (Spearman ρ = 0.416, p = 0.016), whereas no overall directional shift between paired primary and metastatic samples was observed (Wilcoxon signed-rank test: Z = 0.423, p = 0.672). Conclusions: High Cdc42 expression may serve as an adverse prognostic marker in CRC. Cdc42 shows moderate concordance between primary tumors and matched metastases without a consistent directional shift.