Methylation Signature for Prediction of Progression Free Survival in Surgically Treated Clear Cell Renal Cell Carcinoma
| Autor: | Ho Won Kang, Sung Pil Seo, Young Joon Byun, Won-Tae Kim, Sang Cheol Lee, Ho Sun Shon, Hongyong Park, Wooyeong Jang, Sung Min Kim, Keun Ho Ryu, Xuan Mei Piao, Yong-June Kim, Seok Joong Yun, Wun-Jae Kim |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Potassium Channels Urology Kruppel-Like Transcription Factors Nerve Tissue Proteins Methylation 03 medical and health sciences 0302 clinical medicine Risk Factors Renal cell carcinoma Cluster Analysis Humans Medicine Clinical significance 030212 general & internal medicine Progression-free survival Neoplasm Metastasis Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Carcinoma Renal Cell Gene Aged Neoplasm Staging Progression business.industry Renal Cell Carcinoma Membrane Proteins General Medicine DNA Methylation Middle Aged medicine.disease Kidney Neoplasms Progression-Free Survival Repressor Proteins Clear cell renal cell carcinoma DNA methylation Cancer research Female Original Article business Clear cell |
| Zdroj: | Journal of Korean Medical Science |
| ISSN: | 1598-6357 1011-8934 |
| DOI: | 10.3346/jkms.2019.34.e144 |
| Popis: | Background Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). Methods Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. Results Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. Conclusion The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens. Graphical Abstract |
| Databáze: | OpenAIRE |
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