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.
Oncotarget. 2016 Apr 25 [Epub ahead of print]
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
Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China., Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China., Department of Urology, Shaanxi Provincial People's Hospital, Shaanxi, China., Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA., Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China., Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China., Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA., Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China., Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China., Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China., Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA., Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA., Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.