IFI30 Is a Novel Immune-Related Target with Predicting Value of Prognosis and Treatment Response in Glioblastoma
IFI30 Is a Novel Immune-Related Target with Predicting Value of Prognosis and Treatment Response in Glioblastoma
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IFI30 是一种新型免疫相关靶点，具有预测胶质母细胞瘤预后和治疗反应的价值
DOI：
10.2147/ott.s237162
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Wu, Anhua
中科院分区：
文献类型：
--
作者：
Zhu, Chen;Chen, Xin;Wu, Anhua
目的：作为抗肿瘤免疫治疗的重要组成部分，干扰素- α / β (ifn - α / β)治疗已广泛应用于胶质瘤的临床试验。然而，干扰素- γ (ifn - γ)在胶质瘤中的作用尚不清楚。进一步研究ifn - γ家族有价值的中枢分子可能为胶质瘤的治疗提供新的指导。方法：本研究对来自中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）队列的胶质瘤患者进行分析。采用GraphPad Prism 8和R语言进行分析。所有经过验证的实验都独立进行了三次。结果：我们确定IFI30是胶质瘤患者20个经典ifn - γ刺激基因（ISGs）中最稳定的独立预后基因。此外，我们发现IFI30在恶性胶质瘤亚型中高度表达，并与化疗反应相关。我们还通过实验发现IFI30可以激活IL6-STAT6信号通路，从而降低胶质瘤细胞的化疗敏感性。基因本体论（GO）分析显示IFI30与白细胞介导的免疫和炎症反应增强有关。微环境分析显示，IFI30高表达，M2型巨噬细胞浸润增多。结论：IFI30参与了胶质母细胞瘤的恶性进展和化疗反应，可能是胶质母细胞瘤患者治疗的潜在靶点。
Purpose: As a crucial part of anti-tumor immunotherapy, interferon-alpha/beta (IFN-alpha/beta) treatment has been broadly applied to clinical trials of glioma. However, less is known about implement of interferon-gamma (IFN-gamma) in glioma. Further investigating the valuable hub molecular of IFN-gamma family might provide us a novel guidance for glioma therapy.Methods: This study carried out an analysis on glioma patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) cohorts. The analyses were performed by GraphPad Prism 8 and R language. All the validated experiments were performed three times independently.Results: We identified IFI30 as the most stable independent prognostic gene among 20 classical IFN-gamma stimulated genes (ISGs) in glioma patients. Furthermore, we found that IFI30 highly expressed in malignant subtypes of glioma and associated with chemotherapy response. We also found IFI30 could activate IL6-STAT6 signal pathway to decline the glioma cells' chemotherapy sensitivity by performing experiments. Gene ontology (GO) analysis showed IFI30 associated with enhanced leucocyte mediated immune and inflammatory response. Microenvironment analysis referred that high IFI30 expression accompanied with more infiltration of M2 type macrophages.Conclusion: IFI30 is involved in the malignant progression and chemotherapy response of glioblastoma, which can be a potential target for treatment in glioblastoma patients.