Characterization of Prognostic Apoptosis-related Gene Signature to Evaluate Glioma Immune Microenvironment and experimental verification

Abstract

Abstract Purpose Apoptosis-related gene has been demonstrated to modulate the cancer immune in recent studies. Nonetheless, comprehensive roles of apoptosis-related genes in glioma immune microenvironment (GIME) remain unknow. This article was intended to explore the prognostic of apoptosis-related genes in glioma.Methods Doxorubicin was used to induce glioma cells apoptosis, and four differentially expressed apoptosis-related genes were identified, namely CREM, TNFSF12, PEA15 and PRKCD. Kaplan-Meier analyses, receiver operating characteristic curve (ROC) analyses and nomogram were established to construe the relationship between risk markers and the prognosis of glioma patients.Results Risk biomarkers were dramatically associated with overall survival in glioma patients. The high and low risk groups were in relation to immune cell infiltration and immune checkpoints. Somatic mutation and anti-PD-1/L1 immunotherapy demonstrated a worse prognosis in the high-risk group on anti-PD1/PDL1 therapy. In addition, the expression of these four apoptosis-related genes was verified by qPCR and immunohistochemistry, and the relationship between these four genes and apoptosis was examined by flow cytometry.Conclusions This research proclaimed the apoptosis related genes played a critical function in shaping of GIME. Assessing the apoptotic patterns of individual tumors will enhance our understanding of the infiltration feature of GIME and lead better strategies for immunotherapy.