title: Validation of DAB2IP methylation and its relative significance in predicting outcome in renal cell carcinoma.
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.
authors.affiliation: 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.
authors.forename: Zong-Ren
authors.initials: ZR
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
authors.forename: Jin-Huan
authors.initials: JH
authors.lastname: Wei
authors.affiliation: Department of Urology, Shaanxi Provincial People's Hospital, Shaanxi, China.
authors.forename: Jian-Cheng
authors.initials: JC
authors.lastname: Zhou
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haddad
authors.affiliation: Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China.
authors.forename: Liang-Yun
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wu
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, Affiliated Hospital of Kunming University of Science and Technology, Yunnan, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Department of Pathology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liao
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: He
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-sen University, Guangdong, China.
authors.forename: Jun-Hang
authors.initials: JH
authors.lastname: Luo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C462952:DAB2IP protein, human; D020703:ras GTPase-Activating Proteins
keywords: DAB2IP; DNA methylation; intratumour heterogeneity; prognosis; renal cell carcinoma