4.7 Article

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

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SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-022-08346-2

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资金

  1. National Natural Science Foundation of China [82072774, 81872051]
  2. Peking University Clinical Scientist Program [BMU2019LCKXJ007]
  3. Key Clinical Projects of Peking University Third Hospital [BYSY2018060]
  4. China Postdoctoral Science Foundation [2020M670064]
  5. Beijing Natural Science Foundation [7214271]

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This study systematically explored the biological features and clinical significance of CTSB in gliomas. The results showed that CTSB was highly expressed in certain malignant subtypes of gliomas and was an independent hazard associated with poor survival. Additionally, CTSB was found to be involved in immunoreaction and inflammation response in gliomas. The expression of CTSB was positively correlated with inflammatory metagenes and the levels of glioma-infiltrating immune cells, suggesting its potential as a biomarker and therapeutic target for gliomas.
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.

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