Background
It has been reported that 5-methylcytosine (m5C) is involved in DNA/RNA metabolic regulation and has significant implications for cancer diagnosis. M5C-related regulator genes have been reported involved in tumor progression, such as pancreatic adenocarcinomas, low-grade gliomas, and hepatocellular carcinoma, while there have been few studies on the genes in pan-cancers.
Methods
12 m5C-related regulator genes [Y-Box Binding Protein 1 (YBX1), Y-Box Binding Protein 12 (YBX2), NOP2/Sun RNA Methyltransferase 2 (NSUN2), NOP2/Sun RNA Methyltransferase 3 (NSUN3), NOP2/Sun RNA Methyltransferase 4 (NSUN4), NOP2/Sun RNA Methyltransferase 5 (NSUN5), NOP2/Sun RNA Methyltransferase 6 (NSUN6), NOP2/Sun RNA Methyltransferase 27 (NSUN7), DNA Methyltransferase 1 (DNMT1), DNA Methyltransferase 3 Alpha (DNMT3A), DNA Methyltransferase 3 Beta (DNMT3B), tRNA Aspartic Acid Methyltransferase 1 (TRDMT1)] were evaluated for their genomic alterations and clinical relevance across cancers. We performed single nucleotide variations (SNV), copy number variations (CNV), methylation variation, and miRNA-mRNA interactions analysis for patients of 33 cancer types from the Cancer Genome Atlas (TCGA). Based on the Cancer Therapeutics Response Portal (CTRP) and the Genomics of Drug Sensitivity in Cancer (GDSC) database, we assessed the sensitivity of drugs targeting the m5C-related regulator genes.
Results
Several m5C-related regulator genes have undergone significant genetic alterations, and their expression levels are significantly correlated with the activity of cancer hallmark-related pathways. Furthermore, m5C-related regulator genes may serve as used as a prognostic biomarker for cancers. We discovered a number of drugs that may target m5C-related regulator genes by drug sensitivity analysis.
Conclusion
This study revealed the genomic alterations and clinical characteristics of m5C-related regulator genes across 33 cancers, which may clarify the potential mechanism between m5C-related regulator genes and tumorigenesis and provide a novel approach for cancer treatments.