Identification of four key biomarkers and small molecule drugs in nasopharyngeal carcinoma by weighted gene co-expression network analysis

Abstract

Nasopharyngeal carcinoma (NPC) is a heterogeneous carcinoma whose underlying molecular mechanisms involved in tumor initiation, progression, and migration are largely unclear. The aim of the present study was to identify key biomarkers and small-molecule drugs for screening, diagnosing, and treating NPC via gene expression profile analysis. Raw microarray data was used to identify 430 differentially expressed genes (DEGs) in the Gene Expression Omnibus (GEO) database. The key modules associated with histological grade and tumor stage were identified using weighted gene co-expression network analysis. qRT-PCR was used to verify the differential expression of hub genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the connectivity map database were used to identify potential mechanisms and screen small-molecule drugs targeting hub genes. Functional enrichment analysis showed that genes in the green module were enriched in the regulation of cell cycle, p53 signaling pathway, and cell part morphogenesis. Four DEG-related hub genes (CRIP1, KITLG, MARK1, and PGAP1) in the green module, which were considered potential diagnostic biomarkers, were taken as the final hub genes. The expression levels of these four hub genes were verified via qRT-PCR, and the results were consistent with findings from the GEO analysis. Screening was also conducted to identify small-molecule drugs with potential therapeutic effects against NPC. In conclusion, four potential prognostic biomarkers and several candidate small-molecule drugs, which may provide new insights for NPC therapy, were identified.

Keywords

• nasopharyngeal carcinoma
• hub genes
• wgcna
• signature
• small-molecule drugs