A transcriptomic analysis based on aberrant methylation levels revealed potential novel therapeutic targets for nasopharyngeal carcinoma

Ann Transl Med. 2022 Jan;10(2):47. doi: 10.21037/atm-21-6628.

Abstract

Background: This study aimed to identify potential novel therapeutic targets for nasopharyngeal carcinoma (NPC) by identifying aberrantly methylated-differentially expressed genes (DEGs) and pathways based on a comprehensive bioinformatics analysis.

Methods: Eight gene expression data sets and 2 methylation microarray data sets that included NPC and control groups from the Gene Expression Omnibus were identified. Meta-analyses of the DEGs were performed using the online analysis database "NetworkAnalyst". Aberrantly methylated gene loci were obtained from the GEO2R. Aberrantly methylated DEGs were obtained from Venn diagrams. The enrichment analysis was carried out on the "Metascape" website, and the protein-protein interaction (PPI) network construction, network analysis, and visualization of the analysis results were carried out on the "String" website using "Cytoscape" software.

Results: In total, 544 hypomethylation high-expression genes and 164 hypermethylation low-expression genes were obtained. The enrichment and PPI network analyses suggested that several pathways and hub genes with abnormal gene expression accompanied by methylation change, including inositol-trisphosphate 3-kinase B (ITPKB), G protein subunit beta 5 (GNB5), FYN proto-oncogene, Src family tyrosine kinase (FYN), LCK proto-oncogene, Src family tyrosine kinase (LCK), nuclear factor of activated T cells 1 (NFATC1), GNAS complex locus (GNAS), protein kinase C beta (PRKCB), zeta chain of T cell receptor associated protein kinase 70 (ZAP70), lysophosphatidic acid receptor 1 (LPAR1), protein kinase C epsilon (PRKCE), tumor protein p53 (TP53), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fibronectin 1 (FN1), cyclin D1 (CCND1), vascular endothelial growth factor A (VEGFA), HRas proto-oncogene, GTPase (HRAS), signal transducer and activator of transcription 3 (STAT3), fibroblast growth factor 2 (FGF2), amyloid beta precursor protein (APP), and matrix metallopeptidase 2 (MMP2), may be related to the occurrence of nasopharyngeal carcinoma .

Conclusions: The identification of novel and important pathways and hub genes and their roles in the occurrence and development of NPC will guide clinical research and the development of pharmaceutical targets.

Keywords: Gene Expression Omnibus (GEO); Nasopharyngeal carcinoma (NPC); bioinformatics analysis; methylation; transcriptome.