Department of Neurosurgery, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, 119 South 4th Ring Road West, Beijing, 100070, China.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Cancer Immunol Immunother. 2021 Sep;70(9):2589-2600. doi: 10.1007/s00262-021-02865-z. Epub 2021 Feb 12.
Standard treatment regimen of gliomas has almost reached a bottleneck in terms of survival benefit. Immunotherapy has been explored and applied in glioma treatment. Immunosuppression, as a hallmark of glioma, could be alleviated by inhibiting certain abnormally expressed biomarkers. Here, transcriptome data of 325 whole grade gliomas were collected from the CGGA database. The TCGA RNA sequencing database was used for validation. Western blot was used to verify the expression level of VAT1 on cellular level. The results showed that the expression of VAT1 was positively correlated with the grades of glioma as classified by WHO. A higher expression level of VAT1 was observed in the mesenchymal subtype of gliomas. The area under the curve suggested that the expression level of VAT1 might be a potential prognostic marker of mesenchymal subtype. In survival analysis, we found that patients with high VAT1 expression level tended to have shorter overall survival, which indicated the prognostic value of VAT1 expression. The results of gene ontology analysis showed that most biological processes of VAT1-related genes were involved in immune and inflammatory responses. The results of GSEA analysis showed a negative correlation between VAT1 expression and immune cells. We also identified that the expression of immune checkpoints increased with VAT1 expression. Therefore, the high expression level of VAT1 in patients with glioma was a potential indicator of a lower survival rate for patients with gliomas. Remarkably, VAT1 contributed to glioma-induced immunosuppression and might be a novel target in glioma immunotherapy.
标准的脑胶质瘤治疗方案在生存获益方面几乎达到了瓶颈。免疫疗法已经在脑胶质瘤治疗中得到了探索和应用。免疫抑制是脑胶质瘤的一个标志，可以通过抑制某些异常表达的生物标志物来缓解。在这里，我们从 CGGA 数据库中收集了 325 例全级别脑胶质瘤的转录组数据，并在 TCGA RNA 测序数据库中进行了验证。我们使用 Western blot 来验证 VAT1 在细胞水平上的表达水平。结果表明，VAT1 的表达与 WHO 分级的脑胶质瘤呈正相关。在脑胶质瘤的间质亚型中，VAT1 的表达水平更高。曲线下面积表明，VAT1 的表达水平可能是间质亚型的一个潜在预后标志物。在生存分析中，我们发现 VAT1 高表达的患者总体生存时间较短，这表明 VAT1 表达具有预后价值。基因本体论分析的结果表明，VAT1 相关基因的大多数生物学过程都与免疫和炎症反应有关。GSEA 分析的结果表明，VAT1 表达与免疫细胞呈负相关。我们还发现，免疫检查点的表达随着 VAT1 的表达而增加。因此，脑胶质瘤患者中 VAT1 的高表达水平可能是脑胶质瘤患者生存率降低的潜在指标。值得注意的是，VAT1 促进了脑胶质瘤引起的免疫抑制，可能成为脑胶质瘤免疫治疗的一个新靶点。
