Identification of immune‐related hub genes and construction of an immune‐related gene prognostic index for low‐grade glioma

Abstract

AbstractLow‐grade glioma (LGG) poses significant management challenges and has a dismal prognosis. While immunotherapy has shown significant promise in cancer treatment, its progress in glioma has confronted with challenges. In our study, we aimed to develop an immune‐related gene prognostic index (IRGPI) which could be used to evaluate the response and efficacy of LGG patients with immunotherapy. We included a total of 529 LGG samples from TCGA database and 1152 normal brain tissue samples from the GTEx database. Immune‐related differentially expressed genes (DEGs) were screened. Then, we used weighted gene co‐expression network analysis (WGCNA) to identify immune‐related hub genes in LGG patients and performed Cox regression analysis to construct an IRGPI. The median IRGPI was used as the cut‐off value to categorize LGG patients into IRGPI‐high and low subgroups, and the molecular and immune mechanism in IRGPI‐defined subgroups were analysed. Finally, we explored the relationship between IRGPI‐defined subgroups and immunotherapy related indicators in patients after immunotherapy. Three genes (RHOA, NFKBIA and CCL3) were selected to construct the IRGPI. In a survival analysis using TCGA cohort as a training set, patients in the IRGPI‐low subgroup had a better OS than those in IRGPI‐high subgroup, consistent with the results in CGGA cohort. The comprehensive results showed that IRGPI‐low subgroup had a more abundant activated immune cell population and lower TIDE score, higher MSI, higher TMB score, lower T cell dysfunction score, more likely benefit from ICIs therapy. IRGPI is a promising biomarker in the field of LGG ICIs therapy to distinguish the prognosis, the molecular and immunological characteristics of patients.