CDC6 is up-regulated and a poor prognostic signature in glioblastoma multiforme.

Abstract

Glioblastoma multiforme (GBM) represents the most common and the most malignant type of brain tumor. Cell division cycle 6 (CDC6), a gene associated with DNA replication initiation, has been proven to be associated with the prognosis of multiple tumors. In this study, we aim to explore the association between CDC6 expression and GBM carcinogenesis and prognosis. CDC6 expression in normal cells and GBM cells was explored by analyzing TCGA dataset, as well as by RT-PCR and western blot methods. Survival analysis was performed by the Kaplan-Meier method. Multivariate Cox-regression analysis was adopted to estimate the independence of CDC6 as a GBM prognostic factor. Elevated CDC6 levels in GBM tumor tissues compared with those in normal brain tissues were illustrated by analyzing the gene expression profiles from TCGA dataset, and confirmed by RT-PCR and western blot assays in GBM tumor and normal human astrocyte cell lines. Kaplan-Meier analysis indicated the negative influence of high CDC6 expression on GBM overall survival (OS) probability and days to progression (D2P) after initial treatment, but not on days to recurrence (D2R) after initial treatment. Multivariate Cox regression analysis showed CDC6 as an independent signature marker gene for GBM prognosis. In addition, the combination of CDC6 mRNA expression and CpG island methylator phenotype (CIMP) could sensitively predict 3-year OS and D2P. In conclusion, our study uncovered the role of CDC6 in GBM carcinogenesis and prognosis for the first time, which could shed new light on GBM diagnosis and treatment.