title: A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma.
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.
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
authors.forename: Jin-Huan
authors.initials: JH
authors.lastname: Wei
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haddad
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China.
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wu
authors.affiliation: Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong 264000, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhang
authors.affiliation: Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan 650032, China.
authors.forename: Liang-Yun
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Quantitive Biomedical Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Zhou
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Zhou
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan 650032, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Department of Pathology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.affiliation: Department of Pathology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong 510080, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liao
authors.affiliation: School of Mathematics and Computational Science, Sun Yat-sen University, Guangdong 510275, China.
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Li
authors.affiliation: School of Mathematics and Computational Science, Sun Yat-sen University, Guangdong 510275, China.
authors.forename: Pei-Xing
authors.initials: PX
authors.lastname: Li
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
authors.forename: Zong-Ren
authors.initials: ZR
authors.lastname: Wang
authors.affiliation: Department of Urology, Cancer Center, Sun Yat-sen University, Guangdong 510060, China.
authors.forename: Fang-Jian
authors.initials: FJ
authors.lastname: Zhou
authors.affiliation: Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong 264000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong 264000, China.
authors.forename: Qing-Zuo
authors.initials: QZ
authors.lastname: Liu
authors.affiliation: Department of Urology, Affiliated Yantai Yuhuangding Hospital, Qingdao University Medical College, Shandong 264000, China.
authors.forename: Zhen-Li
authors.initials: ZL
authors.lastname: Gao
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, China.
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: He
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Immunology and Microarray Core, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Quan-Zhen
authors.initials: QZ
authors.lastname: Li
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangdong 510080, China.
authors.forename: Jun-Hang
authors.initials: JH
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor