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

Kim,Yong‑June; Jang,Wooyeong; Piao,Xuan‑Mei; Yoon,Hyung‑Yoon; Byun,Young   Joon; Kim,Ji   Sang; Kim,Sung   Min; Lee,Sang   Keun; Seo,Sung   Pil; Kang,Ho  Won; Kim,Won   Tae; Yun,Seok   Joong; Shon,Ho  Sun; Ryu,Keun   Ho; Kim,Sang  Won; Ha,Yun‑Sok; Yoon,Ghil   Suk; Lee,Sang‑Cheol; Kwon,Tae  Gyun; Kim,Wun‑Jae

doi:10.3892/or.2019.7151

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

Authors:
- Yong‑June Kim
- Wooyeong Jang
- Xuan‑Mei Piao
- Hyung‑Yoon Yoon
- Young Joon Byun
- Ji Sang Kim
- Sung Min Kim
- Sang Keun Lee
- Sung Pil Seo
- Ho Won Kang
- Won Tae Kim
- Seok Joong Yun
- Ho Sun Shon
- Keun Ho Ryu
- Sang Won Kim
- Yun‑Sok Ha
- Ghil Suk Yoon
- Sang‑Cheol Lee
- Tae Gyun Kwon
- Wun‑Jae Kim
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Affiliations: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk 28644, Republic of Korea, Clinical Genomics Analysis Branch, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea, Medical Research Institute, School of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk 28644, Republic of Korea, Department of Computer Science, School of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk 28644, Republic of Korea, Department of Urology, School of Medicine, Kyungpook National University, Jung‑gu, Daegu 41944, Republic of Korea, Department of Pathology, School of Medicine, Kyungpook National University, Jung‑gu, Daegu 41944, Republic of Korea
Published online on: May 7, 2019 https://doi.org/10.3892/or.2019.7151
Pages: 453-460

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Abstract

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<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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