Identification of Driver Genes and Key Pathways of Glioblastoma Shows JNJ-7706621 as a Novel Antiglioblastoma Drug

World Neurosurg. 2018 Jan;109:e329-e342. doi: 10.1016/j.wneu.2017.09.176. Epub 2017 Oct 6.

Abstract

Objective: The aim of this study is to identify novel targets of diagnosis, therapy, and prognosis for glioblastoma, as well as to verify the therapeutic effect of JNJ-7706621 regarding glioblastoma.

Methods: The gene expression profiles of GSE42656, GSE50161, and GSE86574 were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified with comparison between gene expression profiles of the glioblastoma tissues and normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analyses were performed. Quantitative reverse transcription polymerase chain reaction and survival curve analysis were also conducted to verify the correlation between expression of hub genes and prognosis. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay, and flow cytometry were performed to verify the therapeutic effect of JNJ-7706621.

Results: AURKA, NDC80, KIF4A, and NUSAP1 were identified as hub genes after PPI network analysis. Differential expression of those genes was detected between human normal glial cells and glioblastoma cells by quantitative reverse transcription polymerase chain reaction (P < 0.05), and the survival curve analysis showed that the patients with low expression of gene AURKA, NDC80, KIF4A, and NUSAP1 had a significant favorable prognosis (P < 0.05). In vitro assays showed that JNJ-7706621 inhibited glioblastoma cellular viability, proliferation, and migration via inducing glioblastoma cells apoptosis.

Conclusions: AURKA, NDC80, KIF4A, and NUSAP1 were significantly more highly expressed in glioblastoma cells than in human normal glial cell. Patients with low expression of those 4 genes had a favorable prognosis. JNJ-7706621 was a potential drug in treatment of patients with glioblastoma.

Keywords: Bioinformatics; Brain science; Drug treatment; Glioma; Prognosis.

MeSH terms

  • Adult
  • Apoptosis / drug effects*
  • Aurora Kinase A / genetics
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Cell Cycle / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Cytoskeletal Proteins
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Humans
  • In Vitro Techniques
  • Kinesin / genetics
  • Male
  • Microtubule-Associated Proteins / genetics
  • Molecular Targeted Therapy
  • Nuclear Proteins / genetics
  • Prognosis
  • Protein Interaction Maps
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Survival Rate
  • Transcriptome
  • Triazoles / pharmacology*
  • Tumor Stem Cell Assay

Substances

  • Cytoskeletal Proteins
  • JNJ-7706621
  • Microtubule-Associated Proteins
  • NDC80 protein, human
  • NUSAP1 protein, human
  • Nuclear Proteins
  • Triazoles
  • AURKA protein, human
  • Aurora Kinase A
  • KIF4A protein, human
  • Kinesin