DNA methylation profiling reveals new potential subtype-specific gene markers for early-stage renal cell carcinoma in Caucasian population

• 作者: Alvaro Filbert Liko Edward Ciputra Nathaniel Alvin Sanjaya Priskila Cherisca Thenaka David Agustriawan
• 来源期刊: 定量生物学（英文版）
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: RESEARCH ARTICLES
• 页码范围: 79-93
• 页数: 15页
• 语种: 英文

摘要

Background:Renal cell carcinoma(RCC)is among the top adult cancers worldwide,with a challenging management due to lack of early diagnosis,therapy resistance,and diverse molecular background.Aberrant DNA methylation has been associated with RCC development due to transcription deregulation.We discovered potential DNA methylation-based biomarkers for stage I RCC in Caucasian population from The Cancer Genome Atlas(TCGA)database.Methods:Patients'clinical,methylation beta-value,and mRNA expression data were retrieved.Differential methy-lation and expression analysis were conducted to obtain differentially methylated CpG-gene pairs.Inversely corre-lated CpG-gene pairs between their expression and methylation levels were selected using Pearson's correlation test and then screened for any recorded somatic mutations.Their biomarker capacities were analyzed using the Kaplan-Meier and receiver operating characteristic analysis,followed by protein network and functional enrichment analysis.Results:We obtained differentially methylated CpGs in clear cell(KIRC)and papillary RCC(KIRP)but not chromophobe RCC(KICH).Six inversely correlated CpG-gene pairs with no reported cancer-associated mutations were selected.Prognostic values were found in ATXN1 and RFTN1 for KIRC,along with GRAMD1B and TM4SF19 for KIRP,while diagnostic values were found in VIM and RFTN1 for KIRC,along with TNFAIP6 and TM4SF19 for KIRP.Both subtypes showed enrichment of immune and metabolism-related pathways.Conclusion:We discovered novel potential DNA methylation-based prognostic and diagnostic markers for early-stage RCC in Caucasian population.Validation by wet laboratory analysis and adjustments for confounding variables might be needed,considering our study limitation to specific race.