Identification of novel genetic and epigenetic regulators of different tissue types of cervical cancer
Abstract
Objectives
The study aimed to find differential gene mutations, DNA methylation, and expression profiles among different categories of cervical cancer samples.
Methods
The study was based on freely available gene mutations, promoter methylation, and gene expression status of The Cancer Genome Atlas (TCGA) cervical cancer samples and adjacent normal tissues in the Genomic Data Commons (GDC) portal. The association of CpG island methylation with gene expression was determined through negative correlation analysis.
Results
We identified that the ErbB signaling pathway and proteoglycans pathway was significantly associated with adenocarcinoma cervical cancers patients. In these pathways, missense mutation especially S310F in theERBB2gene as well as G12D and A146T in theKRASgene were significantly associated with adenocarcinoma cases. Furthermore, a comparison of SCC cases with adjacent control tissues revealed differential hypermethylation of two CpG positions of theKAAG1gene and differential downregulation ofNPY1RandNPY5Rgenes in cervical squamous cell carcinoma compared to cervical adenocarcinoma cases and adjacent normal tissues. Specifically, the hypermethylation of the promoter region of theKAAG1gene might be responsible for the carcinogenesis of cervical squamous cells exclusively and methylation marks can be reversible by the widely used drug, azacytidine. In contrast, adenocarcinoma cervical cancer cases may be treated with floxuridine which is successfully utilized for other tissue‐specific adenocarcinoma cases.
Conclusions
These results provide valuable insight into the differential molecular markers among the categories of cervical cancer, which helps our ability to classify these cancers and for targeted therapy.