Qi Liu1, Kuanyu Wang2, Ruoyu Huang3, Xuezhi Tong4, Tao Jiang1,3, Jiangfei Wang5, Pei Yang6. 1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 2. Gamma Knife Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 3. Department of Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. 4. Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing, China. 5. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. wjf1998@sohu.com. 6. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. peiyang87@163.com.
Abstract
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.
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.
Entities:
Keywords:
Astrocytoma; DNA damage response; Gene signature; Prognosis
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