Abstract
Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.
Highlights
Gliomas are the most common and aggressive primary tumors in adults [1, 2]
Significant association of prognosis with two groups found by hierarchical clustering We selected four microarray and one RNA-seq data sets, which consisted of GSE16011, TCGA, GSE4412 and GSE4271
A stringent threshold cutoff (p < 0.001 and 2.5 fold difference) was applied, and 129 genes whose expression was tightly associated with the two groups were selected (Supplementary Figure S2)
Summary
Gliomas are the most common and aggressive primary tumors in adults [1, 2]. Based on the histological appearance, gliomas can be subdivided into astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas [3]. The response to therapy and the overall survival (OS) of glioma patients varies in different histological subtypes and grades [4]. Oligodendrogliomas have a better prognosis than mixed oligoastrocytomas, and astrocytomas have the worst prognosis [3]. The median survival time is only 1.6 and 0.4 years for grades III www.impactjournals.com/oncotarget and IV gliomas, respectively [5]. Molecular genetic approaches are limited by the heterogeneity within the tumor groups [7]
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