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

  • Oncology
  • Published:
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Abstract

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.

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Abbreviations

AUC:

Area under the curve

ccRCC:

Clear cell RCC

CI:

Confidence interval

HR:

Hazard ratio

NCI:

National Cancer Institute

OR:

Odds ratio

RCC:

Renal cell carcinoma

RUNX3:

Runt-related transcription factor-3

TCIA:

The Cancer Imaging Archive

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Funding

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)

Author information

Author notes

  1. Dongzhi Cen and Li Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong Province, People’s Republic of China

    Dongzhi Cen & Bo Liang

  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 Medicine, 111 Da De Lu, Guangzhou, 510120, Guangdong Province, People’s Republic of China

    Li Xu, Siwei Zhang, Zhiguang Chen, Yan Huang & Ziqi Li

Authors
  1. Dongzhi Cen
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  2. Li Xu
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Corresponding authors

Correspondence to Li Xu or Siwei Zhang.

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The scientific guarantor of this publication is Siwei Zhang.

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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.

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No complex statistical methods were necessary for this paper.

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• retrospective

• prognostic study

• performed at one institution

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Cen, D., Xu, L., Zhang, S. et al. Renal cell carcinoma: predicting RUNX3 methylation level and its consequences on survival with CT features. Eur Radiol 29, 5415–5422 (2019). https://doi.org/10.1007/s00330-019-06049-3

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  • DOI: https://doi.org/10.1007/s00330-019-06049-3

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