Research Papers:

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 and Jun-Hang Luo

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Oncotarget. 2016; 7:31508-31519. https://doi.org/10.18632/oncotarget.8971

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Zong-Ren Wang1,2,*, Jin-Huan Wei1,*, Jian-Cheng Zhou3,*, Ahmed Haddad2,*, Liang-Yun Zhao4, Payal Kapur5, Kai-Jie Wu6, Bin Wang2, Yan-Hong Yu4, Bing Liao7, Da-Lin He6, Wei Chen1, Vitaly Margulis2, Jer-Tsong Hsieh2, Jun-Hang Luo1

1Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China

2Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

3Department of Urology, Shaanxi Provincial People’s Hospital, Shaanxi, China

4Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China

5Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

6Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China

7Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China

*These authors have contributed equally to this work

Correspondence to:

Jer-Tsong Hsieh, email: [email protected]

Jun-Hang Luo, email: [email protected]

Keywords: DAB2IP, DNA methylation, intratumour heterogeneity, prognosis, renal cell carcinoma

Received: October 22, 2015     Accepted: April 02, 2016     Published: April 25, 2016


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.

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