Identification of a Five-mRNA Signature as a Novel Potential Prognostic Biomarker for Glioblastoma by Integrative Analysis

Abstract

Despite the availability of advanced multimodal therapy, the prognosis of patients suffering from glioblastoma (GBM) remains poor. We conducted a genome-wide integrative analysis of mRNA expression profiles in 302 GBM tissues and 209 normal brain tissues from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) project to examine the prognostic and predictive value of specific mRNAs in GBM. A total of 26 mRNAs were identified to be closely related to GBM patients’ OS (p < 0.05). Utilizing survival analysis and the Cox regression model, we discovered a set of five mRNAs (PTPRN, ABCC3, MDK, NMB, and RALYL) from these 26 mRNAs that displayed the capacity to stratify patients into high- and low-risk groups with statistically different overall survival in the training set. The model of the five-mRNA biomarker signature was successfully verified on a testing set and independent sets. Moreover, multivariate Cox regression analysis revealed that the five-mRNA biomarker signature was a prognostic factor for the survival of patients with GBM independent of clinical characteristics and molecular features (p < 0.05). Gene set enrichment analysis indicated that the five-mRNA biomarker signature might be implicated in the incidence and development of GBM through its roles in known cancer-related pathways, signaling molecules, and the immune system. Moreover, consistent with the bioinformatics analysis, NMB, ABCC3, and MDK mRNA expression was considerably higher in four human GBM cells, and the expression of PTPRN and RALYL was decreased in GBM cells (p < 0.05). Our study developed a novel candidate model that provides new prospective prognostic biomarkers for GBM.