ANXA2 is Correlated With the Molecular Features and Clinical Prognosis of Glioma, and Acts as a Potential Marker of Immunosuppression

Abstract Background: Recent studies have shown that ANXA2 plays a crucial role in the development of many cancers, while its role in glioma remains unclear. Thus, our study aimed to investigate the molecular biological characteristics and clinical value of ANXA2 in glioma. Methods: We analyzed the RNA sequencing data of 325 glioma samples from the Chinese Glioma Genome Atlas (CGGA) as the training cohort and the RNA expression data of 699 samples from The Cancer Genome Atlas (TCGA) database as the validation cohort, totaling approximately 1024 samples. Results: We found that ANXA2 was overexpressed significantly in high-grade glioma (HGG), isocitrate dehydrogenase (IDH) wild-type glioma and mesenchymal-subtype glioma. Receiver operating characteristic (ROC) analysis revealed that ANXA2 was a potential indicator of the mesenchymal subtype. Kaplan–Meier curve analysis revealed that high expression of ANXA2 indicated significantly poorer survival in glioma and HGG patients. Multivariate Cox analysis also demonstrated that ANXA2 acted as an independent indicator of poor prognosis in glioma patients. Further gene ontology (GO) analysis showed that ANXA2-related genes were mainly involved in the innate immune response and inflammatory response of glioma, and these genes were positively correlated with the expression of ANXA2. Then, we selected seven immune-related meta-genes and found that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively correlated with IgG. Subsequent correlation analysis of infiltrating immune cells showed that ANXA2 was positively correlated with the infiltration of tumor-related macrophages (TAMs), regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), suggesting that ANXA2 may be involved in the immunosuppression of glioma.Conclusion: Our study revealed that ANXA2 is closely related to the malignant glioma phenotype and poor patient prognosis. ANXA2 also plays an important role in the immune response and inflammatory activity and can be considered a biomarker of immunosuppression in glioma. These findings suggest that ANXA2 may be a promising target for the further development of immunotherapeutic for glioma.