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 smallmolecule 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.

Identification of Key Genes in Nasopharyngeal Carcinoma Based on Bioinformatics Analysis

“…Based on PPI network, seven hub genes that can deeply understand the pathogenesis of NPC at the molecular level are obtained, including FN1, MMP-10, MUC1, KIF23, CDK1, MUC5B, and MUC5AC. Xi et al selected four genes including CRIP1, KITLG, MARK1, and PGAP1 as candidate genes affecting nasopharyngeal carcinoma-based gene expression profile analysis [ 4 ].…”

“…As an efficient and large-scale bioinformation acquisition technology, gene chip can detect and analyze differentially expressed genes (DEGs) between patients and normal humans [ 4 , 5 ]. The analysis of cancer specific gene expression may provide a new research basis for the occurrence and development of human cancer.…”

Virus-host protein co-expression networks reveal temporal organization and strategies of viral infection

“…IRF4 has been shown to facilitate EBV lytic reactivation 45 and is implicated in the differentiation of B cells toward plasma cells associated with many human lymphoid malignancies 46 . CRIP1, on the other hand, is strongly downregulated and has been identified as a biomarker of EBV-associated nasopharyngeal carcinoma 47 . The estrogen receptor-1 protein ESR1 (upregulated), is known to induce the expression of the immediate early viral gene BZLF1 and has been also associated to poor prognosis of nasopharyngeal carcinoma 48 .…”

General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers

“…Previously, the differential expression of CRIP1, KITLG, MARK1, and PGAP1 was identified as a potential prognostic biomarker of NPC [ 34 ]. Ten immune-related genes were identified as prognostic biomarkers of GC [ 35 ].…”

“…SLC26A9 is a member of the solute-linked carrier 26 (SLC26) anion transporter family and is mainly expressed in epithelial cells. SLC26A9 functions uniquely as a chloride channel with minimal conductance to bicarbonate [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. However, the role of SLC26A9 in cancer has not yet been elucidated.…”