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

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

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).

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).

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.