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建立并验证了一种新型基于整合素的预后基因标志物,可对胶质瘤进行亚分类,并能有效预测免疫抑制微环境。

Establishment and validation of a novel integrin-based prognostic gene signature that sub-classifies gliomas and effectively predicts immunosuppressive microenvironment.

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.

Department of Neurosurgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China.

出版信息

Cell Cycle. 2023 May;22(10):1259-1283. doi: 10.1080/15384101.2023.2205204. Epub 2023 Apr 25.

Abstract

The integrin family members play a key role in cancer immunomodulation and prognosis. We comprehensively analyzed the expression patterns and clinical significance of integrin family-related genes in gliomas. A total of 2293 gliomas from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gliovis platform were enrolled for analyses. Twenty-six integrin coding genes showed different expression patterns between glioma and normal brain tissues. We screened an integrin family-related gene signature (ITGA5, ITGA9, ITGAE, ITGB7 and ITGB8) that showed independent prognostic value and sub-classified gliomas into different prognostic and molecular clusters, further composed an integrin-based risk score model associated with glioma malignant clinical features, overall survival (OS), and immune microenvironment alterations. Besides, glioma patients with high-risk scores showed chemotherapeutic resistance and more immune cells infiltration as well as high immune checkpoints expression. Concurrently, we also revealed that high-risk score group presented resistance to T cell-mediated cancer killing process and lower rates of response to immune checkpoint blockade (ICB) treatment. In conclusion, our study identified a valuable integrin gene signature that predicted gliomas OS effectively, and sub-classified them into different phenotypes and accompanied with immunological changes, possibly acted as a biomarker for ICB treatment.

摘要

整合素家族成员在癌症免疫调节和预后中发挥着关键作用。我们全面分析了整合素家族相关基因在脑胶质瘤中的表达模式和临床意义。共纳入了来自癌症基因组图谱(TCGA)、中国脑胶质瘤基因组图谱(CGGA)和 Gliovis 平台的 2293 例脑胶质瘤进行分析。26 个整合素编码基因在脑胶质瘤和正常脑组织之间表现出不同的表达模式。我们筛选出一个整合素家族相关基因特征(ITGA5、ITGA9、ITGAE、ITGB7 和 ITGB8),该特征具有独立的预后价值,并将脑胶质瘤分为不同的预后和分子聚类,进一步构建了一个与脑胶质瘤恶性临床特征、总生存期(OS)和免疫微环境改变相关的基于整合素的风险评分模型。此外,高风险评分的脑胶质瘤患者表现出化疗耐药性以及更多的免疫细胞浸润和高免疫检查点表达。同时,我们还揭示了高风险评分组表现出对 T 细胞介导的癌症杀伤过程的耐药性,以及对免疫检查点阻断(ICB)治疗的反应率较低。总之,我们的研究确定了一个有价值的整合素基因特征,可有效地预测脑胶质瘤的 OS,并将其分为不同的表型,并伴有免疫变化,可能作为 ICB 治疗的生物标志物。

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