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

Jin Huan Wei, Ahmed Haddad, Kai Jie Wu, Hong Wei Zhao, Payal Kapur, Zhi Ling Zhang, Liang Yun Zhao, Zhen Hua Chen, Yun Yun Zhou, Jian Cheng Zhou, Bin Wang, Yan Hong Yu, Mu Yan Cai, Dan Xie, Bing Liao, Cai Xia Li, Pei Xing Li, Zong Ren Wang, Fang Jian Zhou, Lei ShiQing Zuo Liu, Zhen Li Gao, Da Lin He, Wei Chen, Jer Tsong Hsieh, Quan Zhen Li, Vitaly Margulis, Jun Hang Luo

Research output: Contribution to journalArticle

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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 necrosisscores. 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.

Original languageEnglish (US)
Article number8699
JournalNature Communications
Volume6
DOIs
StatePublished - Oct 30 2015

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methylation
Methylation
classifiers
Renal Cell Carcinoma
Assays
Classifiers
cancer
Cells
Survival
genome
Genes
cells
Genome
Atlases
Paraffin
Formaldehyde
prognosis
China
paraffins
stratification

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Wei, J. H., Haddad, A., Wu, K. J., Zhao, H. W., Kapur, P., Zhang, Z. L., ... Luo, J. H. (2015). A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma. Nature Communications, 6, [8699]. https://doi.org/10.1038/ncomms9699

A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma. / Wei, Jin Huan; Haddad, Ahmed; Wu, Kai Jie; Zhao, Hong Wei; Kapur, Payal; Zhang, Zhi Ling; Zhao, Liang Yun; Chen, Zhen Hua; Zhou, Yun Yun; Zhou, Jian Cheng; Wang, Bin; Yu, Yan Hong; Cai, Mu Yan; Xie, Dan; Liao, Bing; Li, Cai Xia; Li, Pei Xing; Wang, Zong Ren; Zhou, Fang Jian; Shi, Lei; Liu, Qing Zuo; Gao, Zhen Li; He, Da Lin; Chen, Wei; Hsieh, Jer Tsong; Li, Quan Zhen; Margulis, Vitaly; Luo, Jun Hang.

In: Nature Communications, Vol. 6, 8699, 30.10.2015.

Research output: Contribution to journalArticle

Wei, JH, Haddad, A, Wu, KJ, Zhao, HW, Kapur, P, Zhang, ZL, Zhao, LY, Chen, ZH, Zhou, YY, Zhou, JC, Wang, B, Yu, YH, Cai, MY, Xie, D, Liao, B, Li, CX, Li, PX, Wang, ZR, Zhou, FJ, Shi, L, Liu, QZ, Gao, ZL, He, DL, Chen, W, Hsieh, JT, Li, QZ, Margulis, V & Luo, JH 2015, 'A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma', Nature Communications, vol. 6, 8699. https://doi.org/10.1038/ncomms9699
Wei, Jin Huan ; Haddad, Ahmed ; Wu, Kai Jie ; Zhao, Hong Wei ; Kapur, Payal ; Zhang, Zhi Ling ; Zhao, Liang Yun ; Chen, Zhen Hua ; Zhou, Yun Yun ; Zhou, Jian Cheng ; Wang, Bin ; Yu, Yan Hong ; Cai, Mu Yan ; Xie, Dan ; Liao, Bing ; Li, Cai Xia ; Li, Pei Xing ; Wang, Zong Ren ; Zhou, Fang Jian ; Shi, Lei ; Liu, Qing Zuo ; Gao, Zhen Li ; He, Da Lin ; Chen, Wei ; Hsieh, Jer Tsong ; Li, Quan Zhen ; Margulis, Vitaly ; Luo, Jun Hang. / A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma. In: Nature Communications. 2015 ; Vol. 6.
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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 necrosisscores. 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.",
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AU - Kapur, Payal

AU - Zhang, Zhi Ling

AU - Zhao, Liang Yun

AU - Chen, Zhen Hua

AU - Zhou, Yun Yun

AU - Zhou, Jian Cheng

AU - Wang, Bin

AU - Yu, Yan Hong

AU - Cai, Mu Yan

AU - Xie, Dan

AU - Liao, Bing

AU - Li, Cai Xia

AU - Li, Pei Xing

AU - Wang, Zong Ren

AU - Zhou, Fang Jian

AU - Shi, Lei

AU - Liu, Qing Zuo

AU - Gao, Zhen Li

AU - He, Da Lin

AU - Chen, Wei

AU - Hsieh, Jer Tsong

AU - Li, Quan Zhen

AU - Margulis, Vitaly

AU - Luo, Jun Hang

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N2 - 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 necrosisscores. 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.

AB - 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 necrosisscores. 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.

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