机构：[1]Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No.58, ZhongShan Second Road, Guangdong 510080, China中山大学附属第一医院[2]Department ofUrology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA[3]Department of Urology, First Affiliated Hospital of Xi’anJiaotong University, Shaanxi 710061, China[4]Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong264000, 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 andTechnology, Yunnan 650032, China[8]Quantitive Biomedical Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas75390, USA[9]Department of Pathology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China[10]Department of Pathology, First AffiliatedHospital, Sun Yat-sen University, Guangdong 510080, China中山大学附属第一医院[11]School of Mathematics and Computational Science, Sun Yat-sen University, Guangdong510275, China[12]Department of Immunology and Microarray Core, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
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 x 10(-6) - 2.2 x 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.
基金：
National Natural Science Foundation of
China (81572905, 81372730, 81225018 and 81372357) and the Guangdong Provincial
Science and Technology Foundation (2014B020212015).
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