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干扰素调节因子转录水平与人类脑胶质瘤的临床结局相关。

Interferon regulatory factor transcript levels correlate with clinical outcomes in human glioma.

机构信息

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Aging (Albany NY). 2021 Apr 26;13(8):12086-12098. doi: 10.18632/aging.202915.

Abstract

Members of the interferon regulatory factor (IRF) gene family are crucial regulators of type I interferon signaling, which may play a role in the resistance of glioma to immune checkpoint blockade. However, the expression profiles, potential functions, and clinical significance of IRF family members remain largely unknown. Here, we examined IRF transcript levels and clinicopathological data from glioma patients using several bioinformatic databases, including ONCOMINE, GEPIA, TCGA, and cBioPortal. We found that IRF1, IRF2, IRF5, IRF8 and IRF9 were significantly upregulated in glioma compared to normal brain tissue. Higher IRF1, IRF2, IRF3, IRF4, IRF5, IRF7, IRF8 and IRF9 mRNA levels correlated with more advanced tumor grades and poorer outcomes. Moreover, although IRFs mutation rates were low (ranging from 0.5% to 2.3%) in glioma patients, genetic alterations in IRFs were associated with more favorable patient survival. Functional analysis showed that IRFs participated in glioma pathology mainly through multiple inflammation- and immunity-related pathways. Additionally, correlations were identified between IRFs and infiltration of immune cells within glioma tissues. Collectively, these results indicate that IRF family members, including IRF1, IRF2, IRF5, IRF8 and IRF9, may serve as prognostic biomarkers and indicators of immune status in glioma patients.

摘要

干扰素调节因子(IRF)基因家族成员是 I 型干扰素信号的关键调节剂,它们可能在胶质瘤对免疫检查点阻断的抵抗中发挥作用。然而,IRF 家族成员的表达谱、潜在功能和临床意义在很大程度上仍不清楚。在这里,我们使用 ONCOMINE、GEPIA、TCGA 和 cBioPortal 等几个生物信息学数据库,检查了胶质瘤患者的 IRF 转录水平和临床病理数据。我们发现,与正常脑组织相比,IRF1、IRF2、IRF5、IRF8 和 IRF9 在胶质瘤中显著上调。更高的 IRF1、IRF2、IRF3、IRF4、IRF5、IRF7、IRF8 和 IRF9 mRNA 水平与更高级别的肿瘤分级和更差的预后相关。此外,尽管胶质瘤患者的 IRFs 突变率较低(范围为 0.5%至 2.3%),但 IRFs 的遗传改变与患者更好的生存相关。功能分析表明,IRFs 主要通过多种炎症和免疫相关途径参与胶质瘤的病理过程。此外,还确定了 IRFs 与胶质瘤组织内免疫细胞浸润之间的相关性。综上所述,这些结果表明,IRF 家族成员(包括 IRF1、IRF2、IRF5、IRF8 和 IRF9)可能作为预测标志物和免疫状态的指标在胶质瘤患者中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a0/8109055/558ad4c95171/aging-13-202915-g001.jpg

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