No abstract

Recent studies have shown that ANXA2 is important in the development of many cancers, while its role in glioma-related immune response remains unclear. We aimed to comprehensively investigate its biological characteristics and clinical value in glioma. We analyzed 699 glioma samples from The Cancer Genome Atlas as training cohort and 325 samples from the Chinese Glioma Genome Atlas as validation cohort. All the statistical analyses and figures were generated with R. ANXA2 was overexpressed significantly in high-grade glioma, isocitrate dehydrogenase wild-type and mesenchymal-subtype glioma. ANXA2 was a special indicator of mesenchymal subtype. The survival analysis showed that highly-expressed ANXA2 was related to worse survival status as an independent factor of poor prognosis. Further gene ontology analysis showed that ANXA2 was mainly involved in immune response and inflammatory activities of glioma. Subsequent correlation analysis showed that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively with IgG. Meanwhile, ANXA2 was positively related to the infiltration of tumor-related macrophages, regulatory T cells and myeloid-derived suppressor cells. Our study revealed that ANXA2 is a biomarker closely related to the malignant phenotype and poor prognosis of glioma, and plays an important role in immune response, inflammatory activity and immunosuppression.

Previous researches have demonstrated the meaning of CTSB for the progress of several tumors, whereas few clues about its immunological characteristic in gliomas. Here we systematically explored its biologic features and clinical significance for gliomas. 699 glioma cases of TCGA and 325 glioma cases of CGGA were respectively included as training and validating cohorts. R software was used for data analysis and mapping. We found that CTSB was remarkably highly-expressed for HGG, IDH wild type, 1p19q non-codeletion type, MGMT promoter unmethylation type and mesenchymal gliomas. CTSB could specifically and sensitively indicate mesenchymal glioma. Upregulated CTSB was an independent hazard correlated with poor survival. CTSB-related biological processes in gliomas chiefly concentrated on immunoreaction and inflammation response. Then we proved that CTSB positively related to most inflammatory metagenes except IgG, including HCK, LCK, MHC II, STAT1 and IFN. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of CTSB, especially for TAMs, MDSCs and Tregs. In conclusion, CTSB is closely related to the malignant pathological subtypes, worse prognosis, immune cells infiltration and immunosuppression of gliomas, which make it a promising biomarker and potential target in the diagnosis, treatment and prognostic assessment of gliomas.