Purpose: The WHO classification for IDH-mutant grade II and grade III astrocytoma may not be as prognostically meaningful as expected. We aimed to develop a novel classification system based on the DNA damage response signature.
Methods: We developed the gene signature of DNA damage response with 115 samples from The Cancer Genome Atlas (TCGA) database. The dataset from Chinese Glioma Genome Atlas (CGGA) database with 41 samples was used as the validation set. Lasso Cox regression model was applied for selection of the best signature. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis were implemented to reveal its biological phenotype.
Results: A two-gene DNA damage response signature (RAD18, MSH2) was developed using the lasso Cox regression model based on the TCGA dataset. Its prognostic efficiency was validated in the CGGA cohort. The result of Cox regression analysis showed that the signature has a better predictive accuracy than the WHO grade. The risk score was an independent prognostic factor for the overall survival of the IDH-mutant grade II and grade III astrocytoma. GSEA and GO analysis confirmed enhanced processes related to DNA damage response in high-risk group.
Conclusion: We developed a two-gene signature which can effectively predict the prognosis of patients with IDH-mutant grade II and grade III astrocytoma. It suggests a novel classification of astrocytoma with better prognostic accuracy based on the expression of DNA damage response genes.
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