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
Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
The China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450000, China.
Discov Oncol. 2023 Aug 29;14(1):161. doi: 10.1007/s12672-023-00765-5.
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.
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.
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.
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.
胶质瘤是一种致命的脑癌，缺乏有效的治疗方法。挑战包括没有有效的治疗靶点、肿瘤内和肿瘤间的异质性、有效药物不足以及免疫抑制微环境等。阐明胶质瘤的发病机制并找出其作用机制对于胶质瘤治疗来说是紧迫且必要的。识别预后生物标志物并靶向这些生物标志物基因将是一种有前景的治疗方法。
从我们对氧化磷酸化（OXPHOS）抑制敏感和OXPHOS抗性细胞系的RNA测序数据中，我们发现支架蛋白小窝蛋白1（CAV1）在抗性组中高表达，而在敏感组中不表达。通过对我们的RNA测序数据、全基因组亚硫酸氢盐测序（WGBS）数据和公共数据库的综合分析，我们发现CAV1在胶质瘤中高表达，并且其表达与病理过程呈正相关，CAV1水平越高，总体生存期越短。
进一步分析表明：（1）CAV1高表达组中的分化基因在免疫浸润和免疫反应中富集；（2）CAV1与肿瘤转移标志物呈正相关；（3）胶质瘤组中CAV1启动子的甲基化水平在高分期时低于低分期；（4）CAV1与胶质瘤干性呈正相关；（5）CAV1的高表达使胶质瘤细胞对氧化磷酸化抑制剂产生抗性。
因此，我们鉴定出一个关键基因CAV1，并阐明了其在胶质瘤进展和预后中的功能，提出CAV1可能是胶质瘤的一个治疗靶点。
