Author:
Liu Yu’e,Chen Yi,Wang Fei,Lin Jianghua,Tan Xiao,Chen Chao,Wu Lei-lei,Zhang Xiaoling,Wang Yi,Shi Yufeng,Yan Xiaoli,Zhao Kaijun
Abstract
Abstract
Background
Glioma is a lethal brain cancer and lacking effective therapies. Challenges include no effective therapeutic target, intra- and intertumoral heterogeneity, inadequate effective drugs, and an immunosuppressive microenvironment, etc. Deciphering the pathogenesis of gliomas and finding out the working mechanisms are urgent and necessary for glioma treatment. Identification of prognostic biomarkers and targeting the biomarker genes will be a promising therapy.
Methods
From our RNA-sequencing data of the oxidative phosphorylation (OXPHOS)-inhibition sensitive and OXPHOS-resistant cell lines, we found that the scaffolding protein caveolin 1 (CAV1) is highly expressed in the resistant group but not in the sensitive group. By comprehensive analysis of our RNA sequencing data, Whole Genome Bisulfite Sequencing (WGBS) data and public databases, we found that CAV1 is highly expressed in gliomas and its expression is positively related with pathological processes, higher CAV1 predicts shorter overall survival.
Results
Further analysis indicated that (1) the differentiated genes in CAV1-high groups are enriched in immune infiltration and immune response; (2) CAV1 is positively correlated with tumor metastasis markers; (3) the methylation level of CAV1 promoters in glioma group is lower in higher stage than that in lower stage; (4) CAV1 is positively correlated with glioma stemness; (5) higher expression of CAV1 renders the glioma cells’ resistant to oxidative phosphorylation inhibitors.
Conclusion
Therefore, we identified a key gene CAV1 and deciphered its function in glioma progression and prognosis, proposing that CAV1 may be a therapeutic target for gliomas.
Graphical Abstract
Funder
the National Natural Science Foundation of China
Science Technology Commission of Shanghai Municipality
Discipline Climbing Scheme
Neuroscience Innovation and Development Research Project
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism