Gene Expression Profiling Stratifies IDH1-Mutant Glioma with Distinct Prognoses

AbstractIsocitrate dehydrogenase (IDH)1 mutation is one of the most important genetic aberrations in glioma. Even several genetic events have refined its prognostic value, the genome-wide expression alteration has not been systematically profiled. In this work, RNA-seq expression data from 310 patients in the Chinese Glioma Genome Atlas database were included as training set, while another 297 patients with microarray data were used as internal validation set. An independent cohort of GSE16011 (n = 205) constituted an external validation set. Approximately one fifth of the genes were differentially expressed in LGG according toIDH1 mutation status, yielding distinct gene expression profiles. A six-gene risk signature was established forIDH1-mutant LGG to distinguish low- from high-risk cases, which had distinct prognoses. The six-gene signature was an independent prognostic factor forIDH1-mutant LGG and had superior predictive value as compared to traditional clinicopathologic factors. Moreover, we depicted the differential expression pattern in GBM attributing to variousIDH1 status, which was similar to that of LGG. It suggested that the effect ofIDH1 mutation is conserved across histological classifications. The six-gene signature had equal prognostic value forIDH1-mutant GBM. By combining glioma grade,IDH1 status, and the six-gene signature, all glioma patients could be classified into six subgroups. These six subgroups could be further summarized into three sets with di...
Source: Molecular Neurobiology - Category: Neurology Source Type: research