ZNF492 and GPR149 methylation patterns as prognostic markers for clear cell renal cell carcinoma: Array‑based DNA methylation profiling

Autor: Ji Sang Kim, Yun-Sok Ha, Xuan Mei Piao, Ho Sun Shon, Sang Cheol Lee, Hyung Yoon Yoon, Seok Joong Yun, Sang-Won Kim, Ghil Suk Yoon, Sang Keun Lee, Ho Won Kang, Sung Min Kim, Yong-June Kim, Keun Ho Ryu, Wooyeong Jang, Sung Pil Seo, Won-Tae Kim, Wun-Jae Kim, Young Joon Byun, Tae Gyun Kwon
Rok vydání: 2019
Předmět:
Zdroj: Oncology Reports.
ISSN: 1791-2431
1021-335X
DOI: 10.3892/or.2019.7151
Popis: 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 cancer‑specific 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. Kaplan‑Meier analysis of TCGA data indicated that only 4/22 loci were significantly associated with disease progression. In the internal validation set, Kaplan‑Meier analysis revealed that hypermethylation of two loci, zinc finger protein 492 (ZNF492) and G protein‑coupled receptor 149 (GPR149), was significantly associated with shorter time‑to‑progression. Multivariate Cox regression models revealed that hypermethylation of ZNF492 [hazard ratio (HR), 5.44; P=0.001] and GPR149 (HR, 7.07; P
Databáze: OpenAIRE