In silico identification of the prognostic biomarkers and therapeutic targets associated with cancer stem cell characteristics of glioma

Biosci Rep. 2020 Aug 28;40(8):BSR20201037. doi: 10.1042/BSR20201037.

Abstract

Glioma is the common histological subtype of malignancy in central nervous system, with a high morbidity and mortality. Cancer stem cells (CSCs) play an important role in regulating the tumorigenesis and progression of glioma; however, the prognostic biomarkers and therapeutic targets associated with CSC characteristics have not been fully acknowledged in glioma. In order to identify the prognostic stemness-related genes (SRGs) of glioma in silico, the RNA sequencing data of patients with glioma were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) was significantly associated with the glioma histologic grade, isocitrate dehydrogenase 1 (IDH1) mutation and overall survival of glioma patients by the nonparametric test and Kaplan-Meier survival analysis. A total of 340 SRGs were identified as the overlapped stemness-related differential expressed genes (DEGs) of different histologic grade screened by the univariate Cox analysis. Based on 11 prognostic SRGs, the predict nomogram was constructed with the AUC of 0.832. Moreover, the risk score of the nomogram was an independent prognostic factor, indicating its significant applicability. Besides other eight reported biomarkers of glioma, we found that F2RL2, CLCNKA and LOXL4 were first identified as prognostic biomarkers for glioma. In conclusion, this bioinformatics study demonstrates the mRNAsi as a reliable index for the IDH1 mutation, histologic grade and OS of glioma patients and provides a well-applied model for predicting the OS for patients with glioma based on prognostic SRGs. Additionally, this in silico study also identifies three novel prognostic biomarkers (F2RL2, CLCNKA and LOXL4) for glioma patients.

Keywords: Cancer stem cells; Glioma; Prediction model; Prognostic biomarker; mRNA expression-based stemness index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Chloride Channels / genetics
  • Chloride Channels / metabolism
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Mutation
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Nomograms
  • Predictive Value of Tests
  • Prognosis
  • Protein-Lysine 6-Oxidase / genetics
  • Protein-Lysine 6-Oxidase / metabolism
  • RNA-Seq
  • Receptors, Thrombin / genetics
  • Receptors, Thrombin / metabolism
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Transcriptome*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CLCNKA protein, human
  • Chloride Channels
  • Receptors, Thrombin
  • protease-activated receptor 3
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • LOXL4 protein, human
  • Protein-Lysine 6-Oxidase