Microarray Analysis of Novel Genes Involved in Nasopharyngeal Carcinoma

Bull Exp Biol Med. 2021 Mar;170(5):658-664. doi: 10.1007/s10517-021-05127-1. Epub 2021 Mar 31.

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial cancer associated with Epstein-Barr virus. Despite NPC is a widespread malignancy, little is known about association of tumor growth with gene expression. This study is aimed to detect potential genes implicated in the molecular mechanism of NPC. To this end, we downloaded GSE12452, GSE53819 and GSE64634 libraries from GEO database. GEO2R interface was used to search for the differentially expressed genes (DEGs) with R and LIMMA software, which yielded the Venn diagrams of co-expressed genes. The GO and KEGG databases were used to find DEGs with up- and down-regulated expression. Then Cytoscape software constructed and analyzed the protein-protein interaction (PPI) networks corresponding to revealed DEGs, thereupon the hub genes were analyzed in tissues and cell cultures with qRT-PCR. This combined analysis yielded 483 co-expressed DEGs, including 258 DEGs with up-regulated expression and 225 DEGs with down-regulated expression, which are mainly implicated in the cell cycle, DNA replication, as well as in formation and maturation of extracellular vesicles and exosomes. In comparison with normal nasopharyngeal tissues of healthy persons, expression of CDK1 gene was down-regulated in NPC tissue; in contrast, expression of PCNA, MAD2L1, PRC1, CENPF, and ZWINT genes was up-regulated in the tumor. The genes PCNA, MAD2L1, and ZWINT were differently expressed in EBV+ and EBV- nasopharyngeal carcinoma cells. The use of bioinformatic methods to reveal and analyze the differences in gene expression between the normal and NPC tissues opens the vista to further progress in deciphering the molecular mechanisms of NPC formation and development.

Keywords: Epstein—Barr virus; bioinformatics; differential gene expression; nasopharyngeal carcinoma.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Computational Biology
  • Epstein-Barr Virus Infections / genetics
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Herpesvirus 4, Human / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mad2 Proteins / genetics
  • Male
  • Microarray Analysis
  • Middle Aged
  • Nasopharyngeal Carcinoma / genetics*
  • Nuclear Proteins / genetics
  • Proliferating Cell Nuclear Antigen / genetics
  • Protein Interaction Maps

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Nuclear Proteins
  • Proliferating Cell Nuclear Antigen
  • ZWINT protein, human