Transcriptome Profile and Clinical Characteristics of CTLA-4 in Diffuse Gliomas

Abstract

CTLA-4, identified as an immune checkpoint, has been widely reported to contribute to downregulation of immune responses to anti-tumor activity. Anti-CTLA-4 provides a novel strategy to improve the outcome of cancer immunotherapy, but the role of CTLA-4 needs to be addressed in glioma. To investigate the role of CTLA-4 in diffuse gliomas, we analyzed the transcriptome level data of CTLA-4 and evaluated its clinical prognostic value. 1022 glioma samples with transcriptome data were enrolled into this study, including 325 RNA-seq data from CGGA and 697 RNA-seq data from TCGA. Clinical and molecular data were also obtained. R project was the main tool for statistical analysis and graphical work. High-grade gliomas exhibited high expression of CTLA-4 while IDH wildtype gliomas showed CTLA-4 enrichment. According to TCGA transcriptional classification in gliomas, mesenchymal subtype displayed significantly higher CTLA-4 expression than other molecular subtypes. Gene ontology analysis demonstrated that CTLA-4 and correlated genes were involved in immune responses and inflammatory activities in diffuse gliomas. Through the analysis of transcriptomic data, CTLA-4 expression strongly correlated with immune cell populations and inflammatory activity. Survival analysis suggested that high expression of CTLA-4 was associated with poor prognosis in gliomas and may serve as an indicator of outcome in gliomas. High CTLA-4 expression is closely related to malignancy in diffuse gliomas and predicts poor outcome. Meanwhile, CTLA-4 plays an important role in regulating T cell activation and antitumor responses in gliomas. Therefore, blocking CTLA-4 is a potential target for developing the immunotherapy of gliomas. Funding: This work was supported by the capital health research and development of special (2014-2-1072); Beijing Municipal Natural Science Foundation (7142054) and National Natural Science Foundation of China (81471229). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This study was approved by Capital Medical University Institutional Review Board (IRB).