Fig 2: The DEGs between WHO grade 4 IDH-mutant astrocytoma and IDH-wildtype GBM and the establishment of 4-gene signature risk-score model. (A) Volcano plot represents the differentially expressed DEGs between WHO grade 4 IDH-mutant astrocytoma and IDH-wildtype GBM, satisfying the criteria of adjusted P-value < 0.05, |log2FC|> 0.5. (B) The Cross-validation fit curve calculated by lasso regression method. (C) LASSO coefficients profiles of DEGs. (D) Multivariate Cox regression analysis of 4 prognostic genes. All 4 genes are protective factors. (E–H) The survival curves of high or low expression of ADD3 (E), GRHPR (F), RHBDL1 (G) and SLC9A9 (H). The survival time of patients with high expression was significantly better than that of patients with low expression of all 4 genes. (I) The expression of ADD3, GRHPR, RHBDL1 and SLC9A9 of WHO grade 4 IDH-mutant astrocytoma and IDH-wildtype GBM patients in GSE121720. IDH mutation group was higher than that in wild group. (J) The relative mRNA expression of ADD3, GRHPR, RHBDL1 and SLC9A9 in U87MG glioma cells. (K) The relative mRNA expression of ADD3, GRHPR, RHBDL1 and SLC9A9 in U251MG glioma cells.

Fig 3: Flowchart for the study. First of all, in vitro, we established two glioma cell lines stably overexpressing IDH1R132H and IDH1wt plasmids. Through the study of radiosensitivity and biological behavior change of the two groups cells, we found that the radiosensitivity of IDH1R132H mutant cells increased and the malignant behavior decreased. Secondly, we enrolled 83 WHO grade 4 glioma patients who received radiotherapy in our center from 2017.1 to 2020.10 to detect IDH1 gene status and analyse differences in PFS and OS. The same patients were enrolled in TCGA and CGGA databases to analyze the correlation between IDH1 gene status and survival. Third, we analyzed the DEGs between IDH1 mutation and IDH1 wild patients in CGGA mRNA microarray data. A 4-gene risk model which can predict the efficacy of radiotherapy was established.