Analysis of complement system gene expression and outcome across the subtypes of glioma

Abstract

Glioma is a malignant and poorly understood cancer that occurs in the glial cells of the brain. Gliomas consist of two clinical subcategories: low-grade glioma (LGG) and glioblastoma (GBM). Based on gene expression profile analysis, gliomas are also divided into four transcriptional subtypes and two mutational subclasses based on IDH expression. These subtypes are associated with differing prognoses, histology, and gene profiles. The complement system, a branch of the innate immune system traditionally associated with inflammation and opsonization, has various pro-tumor effects, including immunosuppression, maintenance of glial stem cells, and hypoxic signaling. We analyzed the expression of complement system genes across the transcriptional and IDH-mutational subtypes of LGG and GBM to determine whether these genes are differentially expressed concerning mutation status and transcriptional subclasses. We performed differential gene expression analysis and analyzed the results for gene set enrichments and correlations with outcome status. The results showed that complement system genes are differentially expressed with varying outcomes across different glioma subtypes. Within the transcriptional subtypes, the complement system genes tended to be overexpressed in subtypes with poor response to treatment or increased tumor malignancy. These results suggest that dysregulation of the complement system may significantly contribute to the categorization of transcriptional subtypes and further, may play a role in treatment response and/or overall patient outcome, although more research is needed to confirm this. These findings could help elucidate the interplay between the immune system, gene expression, and glioma pathogenesis.