Comprehensive analysis of microglia gene and subpathway signatures for glioma prognosis and drug screening: linking microglia to glioma

Abstract

Glioma is the most common malignant tumors in the brain. Previous studies have revealed that, as the innate immune cells in nervous system, microglia cells were involved in glioma pathology. And, the resident microglia displayed its specific biological roles which distinguished with peripheral macrophages. In this study, an integrated analysis was performed based on public resource database to explore specific biological of microglia within glioma. Through comprehensive analysis, the biological characterization underlying two conditions, glioma microglia compared to glioma macrophage (MicT/MacT) as well as glioma microglia compared to normal microglia (MicT/MicN), were revealed. Notably, nine core MicT/MicN genes displayed closely associations with glioma recurrence and prognosis, such as P2RY2, which was analyzed in more than 2800 glioma samples from 25 studies. Furthermore, we applied a random walk based strategy to identify microglia specific subpathways and developed SubP28 signature for glioma prognostic analysis. Multiple validation data sets confirmed the predictive performance of SubP28 and involvement in molecular subtypes. The associations between SuP28 score and microglia M1/M2 polarization were also explored for both GBM and LGG types. Finally, a comprehensive drug-subpathway network was established for screening candidate medicable molecules (drugs) and identifying therapeutic subpathway targets. In conclusions, the comprehensive analysis of microglia related gene and functional signatures in glioma pathobiologic events by large-scale data sets displayed a framework to dissect inner connection between microglia and glioma, and identify robust signature for glioma clinical implications.