Construction of Molecular Subtypes and Related Prognostic and Immune Response Models Based on M2 Macrophages in Glioblastoma

Abstract

Objectives To identify the molecular subtypes of glioblastoma multiforme (GBM) related to M2 macrophage-based prognostic genes, then to preliminarily explore their biological functions and construct immunotherapy response gene models. Material and Methods We used R language to analyze GBM microarray data, and other tools, including xCell and CIBERSORTx, to identify subtypes of GBM that related to M2 macrophages. The process started with the exploration of biological functions of the two subtypes by pathway analyses and GSEA, and continued with a combined procedure of constructing an M2 macrophage-related prognostic gene model and exploring the immune treatment response for GBM. Results A high abundance of M2 macrophages in GBM was associated with poor prognosis. According to M2 macrophage-related prognostic genes, GBM was divided into two subtypes (cluster A and cluster B). The differential gene enrichment analysis of the two clusters showed that cluster A was less enriched in M2 macrophages and had immunopotential. The M2score, which was constructed based on M2 macrophage-related prognostic genes, was not only related to the survival and prognosis of patients with GBM, but also predictive of the effectiveness of immunotherapy in these patients. This result has been effectively verified in an external data set. Conclusion GBM was successfully divided into two subtypes according to M2-macrophage-related prognostic genes. In GBM, a high M2score may indicate better clinical outcome and enhancement of the immunotherapy response.

Downregulated ferroptosis‐related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma

“…GBM is the most common type of grade IV gliomas 46 . Although many tumor treatment have been improved in the past few decades, few effective drugs have been approved by FDA for GBM therapy because of the blood–brain barrier 47 .…”

“…GBM is the most common type of grade IV gliomas. 46 Although many tumor treatment have been improved in the past few decades, few effective drugs have been approved by FDA for GBM therapy because of the blood–brain barrier. 47 Recent studies revealed that immune checkpoint inhibitors appear to be an effective anticancer strategy in glioma immunotherapy.…”

Identification and validation of M2 macrophage-related genes in endometriosis

“…Immune cells with significant differences between the disease group and the control group were found for the subsequent analysis with p.adjust <0.05. Then, the CIBERSORT algorithm [ 22 , 23 ] was further used to verify the difference in the proportion of M2 macrophages between two groups.…”