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基于新型免疫相关基因的特征描述炎症微环境可预测胶质母细胞瘤的预后和放疗疗效

Novel Immune-Related Gene-Based Signature Characterizing an Inflamed Microenvironment Predicts Prognosis and Radiotherapy Efficacy in Glioblastoma.

作者信息

Ji Hang, Zhao Hongtao, Jin Jiaqi, Liu Zhihui, Gao Xin, Wang Fang, Dong Jiawei, Yan Xiuwei, Zhang Jiheng, Wang Nan, Du Jianyang, Hu Shaoshan

机构信息

Department of Neurosurgery, Zhejiang Provincial People's Hospital, Hangzhou, China.

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Genet. 2022 Jan 17;12:736187. doi: 10.3389/fgene.2021.736187. eCollection 2021.

Abstract

Effective treatment of glioblastoma (GBM) remains an open challenge. Given the critical role of the immune microenvironment in the progression of cancers, we aimed to develop an immune-related gene (IRG) signature for predicting prognosis and improving the current treatment paradigm of GBM. Multi-omics data were collected, and various bioinformatics methods, as well as machine learning algorithms, were employed to construct and validate the IRG-based signature and to explore the characteristics of the immune microenvironment of GBM. A five-gene signature (ARPC1B, FCGR2B, NCF2, PLAUR, and S100A11) was identified based on the expression of IRGs, and an effective prognostic risk model was developed. The IRG-based risk model had superior time-dependent prognostic performance compared to well-studied molecular pathology markers. Besides, we found prominent inflamed features in the microenvironment of the high-risk group, including neutrophil infiltration, immune checkpoint expression, and activation of the adaptive immune response, which may be associated with increased hypoxia, epidermal growth factor receptor (EGFR) wild type, and necrosis. Notably, the IRG-based risk model had the potential to predict the effectiveness of radiotherapy. Together, our study offers insights into the immune microenvironment of GBM and provides useful information for clinical management of this desperate disease.

摘要

胶质母细胞瘤(GBM)的有效治疗仍然是一个悬而未决的挑战。鉴于免疫微环境在癌症进展中的关键作用,我们旨在开发一种免疫相关基因(IRG)特征,用于预测预后并改善GBM的当前治疗模式。收集了多组学数据,并采用各种生物信息学方法以及机器学习算法来构建和验证基于IRG的特征,并探索GBM免疫微环境的特征。基于IRG的表达鉴定出一个五基因特征(ARPC1B、FCGR2B、NCF2、PLAUR和S100A11),并开发了一种有效的预后风险模型。与经过充分研究的分子病理学标志物相比,基于IRG的风险模型具有更好的时间依赖性预后性能。此外,我们在高风险组的微环境中发现了显著的炎症特征,包括中性粒细胞浸润、免疫检查点表达和适应性免疫反应的激活,这可能与缺氧增加、表皮生长因子受体(EGFR)野生型和坏死有关。值得注意的是,基于IRG的风险模型有预测放疗效果的潜力。总之,我们的研究为GBM的免疫微环境提供了见解,并为这种难治性疾病的临床管理提供了有用信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a03d/8801921/c808f722c88a/fgene-12-736187-g001.jpg

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