Open AccessDNA methylation profiling reveals new potential subtype‐specific gene markers for early‐stage renal cell carcinoma in Caucasian population
Author(s) -
Liko Alvaro Filbert,
Ciputra Edward,
Sanjaya Nathaniel Alvin,
Thenaka Priskila Cherisca,
Agustriawan David
Publication year - 2022
Publication title -
quantitative biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.707
H-Index - 15
eISSN - 2095-4697
pISSN - 2095-4689
DOI - 10.15302/j-qb-021-0279
Subject(s) - dna methylation , biology , methylation , cpg site , population , differentially methylated regions , cancer research , gene , genetics , gene expression , medicine , environmental health
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 methylation and expression analysis were conducted to obtain differentially methylated CpG‐gene pairs. Inversely correlated 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.