ANXA2 is correlated with the molecular features and clinical prognosis of glioma, and acts as a potential marker of immunosuppression

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.

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

“…In the last few years, TCGA network have divided gliomas into four molecular subtypes: proneural, neural, classical and mesenchymal type 36 . This classification has been proved to be meaningful for patients’ survival status, especially mesenchymal subtype which is representing for invasion and poor prognosis 5 . So, we analyzed the relationship between CTSB and TCGA subtypes.…”

“…In the results above, it is suggested that CTSB is related with the inflammatory response of gliomas, so in order to explore the function of CTSB, we analyzed 104 inflammatory genes which could be divided into seven metagenes 5 . Supplementary Table S3 summarizes the detailed list of these genes.…”

“…To date, even lots of trials of targeted therapy for gliomas have not shown anticipated efficacy, enrichment strategies with more precise biomarkers of gliomas will greatly increase the chances of success in the future 4 , 5 . Our study indicates that highly-expressed CTSB in the immune microenvironment is closely correlated with the malignant molecular features, worse prognosis, immune cells infiltration and immunosuppression processes of gliomas, which can be regard as a new prognostic biomarker and potential therapeutic target.…”

“…Correlation analysis confirmed that glioma-associated immune response and inflammatory activity are significantly correlated with CTSB. Immune cell infiltration and immunosuppression play a vital role in the progression and treatment resistance of gliomas 3 , 5 . But the exact function of CTSB in these processes remains unclear.…”

“…The current therapies for gliomas include surgical resection, chemotherapy, radiation therapy and some other emerging treatments such as molecular targeted therapy, immunotherapy and tumor treating fields (TTF) 2 , 3 . Yet the holistic treatment status of gliomas has achieved limited improvements with these therapies, and the therapeutic response of high-grade gliomas (HGG) is still poor 3 – 5 . More recently, WHO CNS5 has highlight the significance of molecular biomarkers in providing meaningful diagnostic and therapeutic information for gliomas 6 .…”