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

  • Dongzhi Cen
  • Li XuEmail author
  • Siwei ZhangEmail author
  • Zhiguang Chen
  • Yan Huang
  • Ziqi Li
  • Bo Liang



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).


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.

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.


Clear cell renal cell carcinoma Computed tomography Radiogenomics 



Area under the curve


Clear cell RCC


Confidence interval


Hazard ratio


National Cancer Institute


Odds ratio


Renal cell carcinoma


Runt-related transcription factor-3


The Cancer Imaging Archive



Supported by Guangdong Science and Technology Project (2016ZC0142), the project for the Social Development Project of Dongguan City (2015108101032), and Medical Scientific Research Foundation of Guangdong Province (A2016391)

Compliance with ethical standards


The scientific guarantor of this publication is Siwei Zhang.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was not required for this study.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• prognostic study

• performed at one institution

Supplementary material

330_2019_6049_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)


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Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyThe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouPeople’s Republic of China
  2. 2.The Second Affiliated Hospital of Guangzhou University of Chinese Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine & Guangdong Provincial Hospital of Chinese MedicineGuangzhouPeople’s Republic of China

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