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通过综合生物信息学分析鉴定胰岛素受体相关受体(INSRR)为胶质母细胞瘤肿瘤微环境中的免疫相关基因。

Identification of INSRR as an immune-related gene in the tumor microenvironment of glioblastoma by integrated bioinformatics analysis.

作者信息

Zhang Haofuzi, Bao Mingdong, Liao Dan, Zhang Zhuoyuan, Tian Zhicheng, Yang Erwan, Luo Peng, Jiang Xiaofan

机构信息

Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an No. 127, Changle West Road, Xincheng District, Xi'an, Shaanxi Province, China.

Biochemistry and Molecular Biology, College of Life Science, Northwest University, Xi'an, 710127, Shaanxi Province, China.

出版信息

Med Oncol. 2023 Apr 26;40(6):161. doi: 10.1007/s12032-023-02023-8.

Abstract

Gliomas are the most common malignant tumors in the central nervous system. The tumor microenvironment (TME) plays a crucial role in tumor proliferation, invasion, angiogenesis, and immune escape. However, little is known about TME in gliomas. The purpose of this study was to explore the biomarkers associated with TME in glioblastoma (GBM) to predict immunotherapy effectiveness and prognosis in patients. Based on RNA-seq transcriptome data and clinical features of 1222 samples (113 normal samples and 1109 tumor samples) in The Cancer Genome Atlas (TCGA) database, the ImmuneScore, StromalScore, and ESTIMATEScore were calculated by ESTIMATE algorithm. The differentially expressed genes (DEGs) and differentially mutated genes (DMGs) were determined in the TCGA GBM cohort. Furthermore, gene set enrichment analysis (GSEA) was used to investigate the enrichment pathways of INSRR genes with abnormal expression. The proportion of tumor-infiltrating immune cells (TIICs) was evaluated by CIBERSORT. Frequent mutations of TP53, EGFR, and PTEN occurred in high and low immune scores. The cross-analysis of DEGs and DMGs revealed that INSRR was an immune-related biomarker in the TCGA GBM cohort. According to GSEA, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway with INSRR abnormal expression were IgA-produced intestinal immune network and Alzheimer's disease, oxidative phosphorylation, and Parkinson's disease, respectively. Additionally, INSRR expression was correlated with dendritic cells activated, dendritic cells resting, T cells CD8, and T cell gamma delta. INSRR is associated with the immune microenvironment in GBM and is used as a biomarker to predict immune invasion.

摘要

神经胶质瘤是中枢神经系统中最常见的恶性肿瘤。肿瘤微环境(TME)在肿瘤增殖、侵袭、血管生成和免疫逃逸中起着关键作用。然而,人们对神经胶质瘤中的TME了解甚少。本研究的目的是探索与胶质母细胞瘤(GBM)中TME相关的生物标志物,以预测患者的免疫治疗效果和预后。基于癌症基因组图谱(TCGA)数据库中1222个样本(113个正常样本和1109个肿瘤样本)的RNA测序转录组数据和临床特征,通过ESTIMATE算法计算免疫评分、基质评分和ESTIMATE评分。在TCGA GBM队列中确定差异表达基因(DEG)和差异突变基因(DMG)。此外,基因集富集分析(GSEA)用于研究INSRR基因异常表达的富集途径。通过CIBERSORT评估肿瘤浸润免疫细胞(TIIC)的比例。TP53、EGFR和PTEN的频繁突变发生在高免疫评分和低免疫评分中。DEG和DMG的交叉分析表明,INSRR是TCGA GBM队列中的一种免疫相关生物标志物。根据GSEA,INSRR异常表达的京都基因与基因组百科全书(KEGG)途径分别是IgA产生的肠道免疫网络和阿尔茨海默病、氧化磷酸化和帕金森病。此外,INSRR表达与活化的树突状细胞、静息的树突状细胞、CD8 T细胞和γδ T细胞相关。INSRR与GBM中的免疫微环境相关,并用作预测免疫侵袭的生物标志物。

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