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Nat Commun. 2015 Oct 30;6:8699. doi: 10.1038/ncomms9699.

A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma.

Author information

1
Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
2
Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
3
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China.
4
Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong 264000, China.
5
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
6
Department of Urology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
7
Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan 650032, China.
8
Quantitive Biomedical Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
9
Department of Pathology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
10
Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong 510080, China.
11
School of Mathematics and Computational Science, Sun Yat-sen University, Guangdong 510275, China.
12
Department of Immunology and Microarray Core, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.

Abstract

Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96-4.82; P=3.9 × 10(-6)-2.2 × 10(-9)), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual 'stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system.

PMID:
26515236
PMCID:
PMC4846314
DOI:
10.1038/ncomms9699
[Indexed for MEDLINE]
Free PMC Article

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