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MYD88是胶质瘤肿瘤微环境的潜在预后基因和免疫标志物。

MYD88 Is a Potential Prognostic Gene and Immune Signature of Tumor Microenvironment for Gliomas.

作者信息

Guo Qinglong, Xiao Xing, Zhang Jinsen

机构信息

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Neurosurgery Department of Huashan Hospital, Neurosurgical Institute of Fudan University, Shanghai, China.

出版信息

Front Oncol. 2021 Apr 7;11:654388. doi: 10.3389/fonc.2021.654388. eCollection 2021.

Abstract

PURPOSE

To explore the profiles of immune and stromal components of the tumor microenvironment (TME) and their related key genes in gliomas.

METHODS

We applied bioinformatic techniques to identify the core gene that participated in the regulation of the TME of the gliomas. And immunohistochemistry staining was used to calculate the gene expressions in clinical cases.

RESULTS

The CIBERSORT and ESTIMATE were used to figure out the composition of TME in 698 glioma cases from The Cancer Genome Atlas (TCGA) database. Differential expression analysis identified 2103 genes between the high and the low-score group. Then the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, univariate Cox regression analysis, and protein-protein interaction (PPI) network construction were conducted based on these genes. MYD88 was identified as the key gene by the combination univariate Cox and PPI analysis. Furthermore, MYD88 expression was significantly associated with the overall survival and WHO grade of glioma patients. The genes in the high-expression MYD88 group were mainly in immune-related pathways in the Gene Set Enrichment Analysis (GSEA). We found that macrophage M2 accounted for the largest portion with an average of 27.6% in the glioma TIICs and was associated with high expression of MYD88. The results were verified in CGGA database and clinical cases in our hospital. Furthermore, we also found the MYD88 expression was higher in IDH1 wild types. The methylation rate was lower in high grade gliomas.

CONCLUSION

MYD88 had predictive prognostic value in glioma patients by influencing TIICs dysregulation especially the M2-type macrophages.

摘要

目的

探讨神经胶质瘤肿瘤微环境(TME)的免疫和基质成分特征及其相关关键基因。

方法

我们应用生物信息学技术鉴定参与神经胶质瘤TME调控的核心基因。并采用免疫组织化学染色计算临床病例中的基因表达。

结果

使用CIBERSORT和ESTIMATE分析来自癌症基因组图谱(TCGA)数据库的698例神经胶质瘤病例的TME组成。差异表达分析确定了高分和低分两组之间的2103个基因。然后基于这些基因进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析、单变量Cox回归分析和蛋白质-蛋白质相互作用(PPI)网络构建。通过单变量Cox和PPI分析相结合,确定MYD88为关键基因。此外,MYD88表达与神经胶质瘤患者的总生存期和世界卫生组织(WHO)分级显著相关。在基因集富集分析(GSEA)中,高表达MYD88组中的基因主要参与免疫相关途径。我们发现巨噬细胞M2在神经胶质瘤肿瘤浸润免疫细胞(TIICs)中占比最大,平均为27.6%,且与MYD88的高表达相关。结果在CGGA数据库和我院临床病例中得到验证。此外,我们还发现MYD88在异柠檬酸脱氢酶1(IDH1)野生型中表达较高。高级别神经胶质瘤中的甲基化率较低。

结论

MYD88通过影响TIICs失调,尤其是M2型巨噬细胞,对神经胶质瘤患者具有预测预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/737e/8059377/52e6f5f7779b/fonc-11-654388-g001.jpg

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