Validation of DAB2IP methylation and its relative significance in predicting outcome in renal cell carcinoma

Zong Ren Wang, Jin Huan Wei, Jian Cheng Zhou, Ahmed Haddad, Liang Yun Zhao, Payal Kapur, Kai Jie Wu, Bin Wang, Yan Hong Yu, Bing Liao, Da Lin He, Wei Chen, Vitaly Margulis, Jer Tsong Hsieh, Jun Hang Luo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

We have recently reported tumor suppressive role of DAB2IP in RCC development. In this study, We identified one CpG methylation biomarker (DAB2IP CpG1) located UTSS of DAB2IP that was associated with poor overall survival in a cohort of 318 ccRCC patients from the Cancer Genome Atlas (TCGA). We further validated the prognostic accuracy of DAB2IP CpG methylation by pyrosequencing quantitative methylation assay in 224 ccRCC patients from multiple Chinese centers (MCHC set), and 239 patients from University of Texas Southwestern Medical Center at Dallas (UTSW set) by using FFPE samples. DAB2IP CpG1 can predict the overall survival of patients in TCGA, MCHC, and UTSW sets independent of patient age, Fuhrman grade and TNM stage (all p < 0.05). DAB2IP CpG1 successfully categorized patients into high-risk and low-risk groups with significant differences of clinical outcome in respective clinical subsets, regardless of age, sex, grade, stage, or race (HR: 1.63-7.83; all p < 0.05). The detection of DAB2IP CpG1 methylation was minimally affected by ITH in ccRCC. DAB2IP mRNA expression was regulated by DNA methylation in vitro. DAB2IP CpG1 methylation is a practical and repeatable biomarker for ccRCC, which can provide prognostic value that complements the current staging system.

Original languageEnglish (US)
Pages (from-to)31508-31519
Number of pages12
JournalOncotarget
Volume7
Issue number21
DOIs
StatePublished - May 24 2016

Keywords

  • DAB2IP
  • DNA methylation
  • Intratumour heterogeneity
  • Prognosis
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology

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