[No authors listed]
The present study aimed to identify novel methylation markers of clear cell renal cell carcinoma (ccRCC) using microarray methylation analysis and evaluate their prognostic relevance in patient samples. To identify cancerâspecific methylated biomarkers, microarray profiling of ccRCC samples from our institute (n=12) and The Cancer Genome Atlas (TCGA) database (n=160) were utilized, and the prognostic relevance of candidate genes were investigated in another TCGA dataset (n=153). For validation, pyrosequencing analyses with ccRCC samples from our institute (n=164) and another (n=117) were performed and the potential clinical application of selected biomarkers was examined. We identified 22 CpG island loci that were commonly hypermethylated in ccRCC. KaplanâMeier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, KaplanâMeier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G proteinâcoupled receptor 149 (GPR149), was significantly associated with shorter timeâtoâprogression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P<0.001) may be independent predictors of tumor progression. Similarly, the methylation status of these two genes was significantly associated with poor outcomes in the independent external validation cohort. Collectively, the present study proposed that the novel methylation markers ZNF492 and GPR149 could be independent prognostic indicators in patients with ccRCC.
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