Construction of co-expression modules related to survival by WGCNA and identification of potential prognostic biomarkers in glioblastoma.

Abstract

Glioblastoma (GBM) is a malignant brain tumour with poor prognosis. The potential pathogenesis and therapeutic target are still need to be explored. Herein, TCGA expression profile data and clinical information were downloaded, and the WGCNA was conducted. Hub genes which closely related to poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM, and immune microenvironment were analysed. Patients from TCGA were divided into high‐ and low‐risk group. WGCNA was applied to the high‐ and low‐risk group and the black module with the lowest preservation was identified which could distinguish the prognosis level of these two groups. The top 10 hub genes which were closely related to poor prognosis of patients were obtained. GO analysis showed the biological process of these genes mainly enriched in: Cell cycle, Progesterone‐mediated oocyte maturation and Oocyte meiosis. CDCA5 and CDCA8 were screened out as the genes of interest. We found that their expression levels were closely related to overall survival. The difference analysis resulted from the TCGA database proved both CDCA5 and CDCA8 were highly expressed in GBM. After transfection of U87‐MG cells with small interfering RNA, it revealed that knockdown of the CDCA5 and CDCA8 could influence the biological behaviours of proliferation, clonogenicity and apoptosis of GBM cells. Then, single‐gene analysis was performed. CDCA5 and CDCA8 both had good correlations with genes that regulate cell cycle in the p53 signalling pathway. Moreover, it revealed that high amplification of CDCA5 was correlated with CD8+ T cells while CDCA8 with CD4+ T cells in GBM. These results might provide new molecular targets and intervention strategy for GBM.