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

49 Scopus citations

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

ASJC Scopus subject areas

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

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    Wei, J. H., Haddad, A., Wu, K. J., Zhao, H. W., Kapur, P., Zhang, Z. L., Zhao, L. Y., Chen, Z. H., Zhou, Y. Y., Zhou, J. C., Wang, B., Yu, Y. H., Cai, M. Y., Xie, D., Liao, B., Li, C. X., Li, P. X., Wang, Z. R., Zhou, F. J., ... 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