Identification of Prognostic Biomarkers of Glioblastoma Based on Multidatabase Integration and Its Correlation with Immune-Infiltration Cells

Abstract

Background. Glioblastoma (GBM) is the most malignant of all known intracranial tumors; meanwhile, most patients have a poor prognosis. In order to improve the poor prognosis of GBM patients as much as possible, it is specifically significant to identify biomarkers related to the gene diagnosis and gene therapy. Methods. In this study, a total of 343 GBM specimens and 259 nontumor specimens were collected from four Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database; then, we analyzed the differentially expressed genes (DEGs) from the above data. Through Venn diagram analysis, 54 common upregulated DEGs and 22 common downregulated DEGs were triumphantly recognized. Results. On the basis of the degree of formation communication in protein-protein interaction network (PPIN), the 10 upregulated central genes were ranked, incorporating LOX, IGFBP3, CD44, TIMP1, FN1, VEGFA, POSTN, COL1A1, COL1A2, and COL3A1. By combining the expression levels and the clinical features of GBM, we found that four hub genes (TIMP1, FN1, POSTN, and LOX) were significantly upregulated and related to poor prognosis of GBM. Meanwhile, univariate and multivariate Cox regression analysis suggested that TIMP1 could be one of the independent prognostic factors for GBM patients. Furthermore, TIMP1 was particularly correlated with the immune marker of macrophage M1, macrophage M2, neutrophils, tumor-associated macrophage, and Tregs. We then analyzed the role of TIMP1 in GBM cancer cell lines by relevant experiments, which indicated that TIMP1 knockdown resulted in the decreased cell proliferation, migration, and invasion. Conclusions. Taken together, these findings demonstrated that TIMP1 might be a new biomarker to determine prognosis and immune infiltration of GBM patients.