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A Two-DNA Methylation Signature to Improve Prognosis Prediction of Clear Cell Renal Cell Carcinoma

Yonsei Medical Journal 2019년 60권 11호 p.1013 ~ 1020
 ( Shi Shanping ) - Ningbo University Medical School Institute of Biochemistry and Molecular Biology

 ( Ye Shazhou ) - Ningbo University Medical School Institute of Biochemistry and Molecular Biology
 ( Wu Xiaoyue ) - Ningbo University Medical School Institute of Biochemistry and Molecular Biology
 ( Xu Mingjun ) - Ningbo University Medical School Institute of Biochemistry and Molecular Biology
 ( Zhuo Renjie ) - Ningbo University Medical School Department of Preventative Medicine
 ( Liao Qi ) - Ningbo University Medical School Department of Preventative Medicine
 ( Xi Yang ) - Ningbo University Medical School Institute of Biochemistry and Molecular Biology

Abstract


Purpose: Effective biomarkers and models are needed to improve the prognostic prospects of clear cell renal cell carcinoma (ccRCC). The purpose of this work was to identify DNA methylation biomarkers and to evaluate the utility of DNA methylation analysis for ccRCC prognosis.

Materials and Methods: An overview of genome-wide methylation of ccRCC tissues derived from The Cancer Genome Atlas (TCGA) database was download for analysis. DNA methylation signatures were identified using Cox regression methods. The potential clinical significance of methylation biomarkers acting as a novel prognostic markers was analyzed using the Kaplan-Meier method and receiver operating characteristic (ROC) curves.

Results: This study analyzed data for 215 patients with information on 23171 DNA methylation sites and identified a two-DNA methylation signature (cg18034859, cg24199834) with the help of a step-wise multivariable Cox regression model. The area under the curve of ROCs for the two-DNA methylation signature was 0.819. The study samples were stratified into low- and high-risk classifications based on an optimal threshold, and the two groups showed markedly different survival rates. Moreover, the two-DNA methylation marker was suitable for patients of varying ages, sex, stages (I and IV), and histologic grade (G2).

Conclusion: The two-DNA methylation signature was deemed to be a potential novel prognostic biomarker of use in increasing the accuracy of predicting overall survival of ccRCC patients.

키워드

Carcinoma; renal cell; biomarkers; DNA methylation; prognosis
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