Exploring the Epigenome and Transcriptome to Identify Biomarkers in Ovarian Cancer

Abstract

DNA methylation plays a vital role in cancer by regulating gene transcription. Alteration in DNA methylation among some genes has been associated with various tumors and this change in methylation signature among various genes can be potentially used as a biomarker for cancer detection. In the current work the Cancer Genome Atlas (TCGA) database was assessed for alterations in DNA methylation of 1816 genes in 600 ovarian cancer patients and 8 healthy subjects. Clustering of methylation patterns showed 5 major patient clusters.  Alteration in methylation and gene expression of known biomarkers BRCA1, IQGAP1, BLCAP, MSH2, HSF1 along with novel biomarkers hSulf1 and HMSH2 was assessed in the ovarian cancer and normal subjects.  The methylation levels were differentially expressed compared to healthy subjects.  Compared to normal subjects, in ovarian cancer patients hSulf1, BRCA1, HSF1, BLCAP were hypomethylated while genes IQGAP1 and MSH2 were hypermethylated.  The methylation levels for the specific genes considered biomarkers above were correlated with their mRNA expression level to see if there is an association between mRNA expression and methylation levels.  Genes hSulf1, BRCA1, HSF1, IQGAP1 were negatively correlated with their methylation levels while MSH2 and BLCAP were positively correlated in ovarian cancer patients.  Our study showed specific gene methylation clusters among the ovarian cancer patients suggesting this could potentially be used as a signature. In Cancer patients, methylation was significantly altered, and this alteration was correlated with its gene transcription.