Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China.
Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing, 100191, China.
J Mol Neurosci. 2020 Oct;70(10):1501-1511. doi: 10.1007/s12031-020-01583-y. Epub 2020 Jun 3.
Diffuse glioma is the deadliest form of brain cancer, and the median survival of grade IV glioma (glioblastoma, GBM) is no more than 2 years even with maximal surgical resection followed by radiotherapy and chemotherapy, which are now the standard of care for GBM. Glioma shares common characteristics with most malignant tumours, such as invasiveness, rapid progression, resistance to various therapies and inevitable recurrence, while it also has its own unique features, such as high aggressiveness and immunotherapy resistance, which can be, respectively, attributed to epithelial-mesenchymal transition (EMT) and the immunosuppressive microenvironment. Here, we calculated the EMT score of glioma using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Omnibus (GEO) datasets and validated its prognostic value. Then, we investigated its role in the glioma immune microenvironment, identified the enriched EMT-related immune genes and determined their specific biological functions in glioma. Furthermore, clinical relevance analysis showed the translational value of these EMT-related immune genes. In short, our findings reveal a critical link between EMT and the glioma immune microenvironment and offer important clues for further investigation of the underlying molecular mechanism.
弥漫性神经胶质瘤是最致命的脑癌形式，即使在最大限度的手术切除后进行放疗和化疗，IV 级神经胶质瘤（胶质母细胞瘤，GBM）的中位生存期也不超过 2 年，目前这是 GBM 的标准治疗方法。神经胶质瘤与大多数恶性肿瘤具有共同特征，如侵袭性、快速进展、对各种治疗的耐药性和不可避免的复发，同时它也具有自身独特的特征，如高侵袭性和免疫治疗耐药性，这可分别归因于上皮-间充质转化（EMT）和免疫抑制微环境。在这里，我们使用癌症基因组图谱（TCGA）、中国神经胶质瘤基因组图谱（CGGA）和基因表达综合数据库（GEO）数据集计算了神经胶质瘤的 EMT 评分，并验证了其预后价值。然后，我们研究了其在神经胶质瘤免疫微环境中的作用，确定了富含 EMT 相关的免疫基因，并确定了它们在神经胶质瘤中的特定生物学功能。此外，临床相关性分析显示了这些 EMT 相关免疫基因的转化价值。总之，我们的研究结果揭示了 EMT 与神经胶质瘤免疫微环境之间的关键联系，并为进一步研究潜在的分子机制提供了重要线索。
