Multi-Omics Data Integration Analysis of an Immune-Related Gene Signature in LGG Patients With Epilepsy

Abstract

BackgroundThe tumor immune microenvironment significantly affects tumor occurrence, progression, and prognosis, but its impact on the prognosis of low-grade glioma (LGG) patients with epilepsy has not been reported. Hence, the purpose of this study is to explore its effect on LGG patients with epilepsy.MethodsThe data of LGG patients derived from the TCGA database. The level of immune cell infiltration and the proportion of 22 immune cells were evaluated by ESTIMATE and CIBERSORT algorithms, respectively. The Cox and LASSO regression analysis was adopted to determine the DEGs, and further established the clustering and risk score models. The association between genomic alterations and risk score was investigated using CNV and somatic mutation data. GSVA was adopted to identify the immunological pathways, immune infiltration and inflammatory profiles related to the signature genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and GDSC database were used to predict the patient’s response to immunotherapy and chemotherapy, respectively.ResultsThe prognosis of LGG patients with epilepsy was associated with the immune score. Three prognostic DEGs (ABCC3, PDPN, and INA) were screened out. The expression of signature genes was regulated by DNA methylation. The clustering and risk score models could stratify glioma patients into distinct prognosis groups. The risk score was an independent predictor in prognosis, with a high risk-score indicating a poor prognosis, more malignant clinicopathological and genomic aberration features. The nomogram had the better predictive ability. Patients at high risk had a higher level of macrophage infiltration and increased inflammatory activities associated with T cells and macrophages. While the higher percentage of NK CD56bright cell and more active inflammatory activity associated with B cell were present in the low-risk patients. The signature genes participated in the regulation of immune-related pathways, such as IL6-JAK-STAT3 signaling, IFN-α response, IFN-γ response, and TNFA-signaling-via-NFKB pathways. The high-risk patients were more likely to benefit from anti-PD1 and temozolomide (TMZ) treatment.ConclusionAn immune-related gene signature was established based on ABCC3, PDPN, and INA, which can be used to predict the prognosis, immune infiltration status, immunotherapy and chemotherapy response of LGG patients with epilepsy.