Renal cell carcinoma: predicting RUNX3 methylation level and its consequences on survival with CT features.

Purpose: To investigate associations between CT imaging features, RUNX3 methylation level, and survival in clear cell renal cell carcinoma (ccRCC).

Materials And Methods: Patients were divided into high RUNX3 methylation and low RUNX3 methylation groups according to RUNX3 methylation levels (the threshold was identified by using X-tile). The CT scanning data from 106 ccRCC patients were retrospectively analyzed. The relationship between RUNX3 methylation level and overall survivals was evaluated using the Kaplan-Meyer analysis and Cox regression analysis (univariate and multivariate). The relationship between RUNX3 methylation level and CT features was evaluated using chi-square test and logistic regression analysis (univariate and multivariate).

Results: β value cutoff of 0.53 to distinguish high methylation (N = 44) from low methylation tumors (N = 62). Patients with lower levels of methylation had longer median overall survival (49.3 vs. 28.4) months (low vs. high, adjusted hazard ratio [HR] 4.933, 95% CI 2.054-11.852, p < 0.001). On univariate logistic regression analysis, four risk factors (margin, side, long diameter, and intratumoral vascularity) were associated with RUNX3 methylation level (all p < 0.05). Multivariate logistic regression analysis found that three risk factors (side: left vs. right, odds ratio [OR] 2.696; p = 0.024; 95% CI 1.138-6.386; margin: ill-defined vs. well-defined, OR 2.685; p = 0.038; 95% CI 1.057-6.820; and intratumoral vascularity: yes vs. no, OR 3.286; p = 0.008; 95% CI 1.367-7.898) were significant independent predictors of high methylation tumors. This model had an area under the receiver operating characteristic curve (AUC) of 0.725 (95% CI 0.623-0.827).

Conclusions: Higher levels of RUNX3 methylation are associated with shorter survival in ccRCC patients. And presence of intratumoral vascularity, ill-defined margin, and left side tumor were significant independent predictors of high methylation level of RUNX3 gene.

Key Points: • RUNX3 methylation level is negatively associated with overall survival in ccRCC patients. • Presence of intratumoral vascularity, ill-defined margin, and left side tumor were significant independent predictors of high methylation level of RUNX3 gene.