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 |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Candidate gene Microarray Biology Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Internal medicine Biomarkers Tumor medicine Carcinoma Humans Carcinoma Renal Cell Aged Oligonucleotide Array Sequence Analysis Aged 80 and over Sequence Analysis DNA General Medicine Methylation Middle Aged Prognosis medicine.disease Survival Analysis Kidney Neoplasms DNA-Binding Proteins Clear cell renal cell carcinoma 030104 developmental biology CpG site Tumor progression 030220 oncology & carcinogenesis DNA methylation Disease Progression CpG Islands Female Transcription Factors |
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 |
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