Elevated TYROBP expression predicts poor prognosis and high tumor immune infiltration in patients with low-grade glioma.
Elevated TYROBP expression predicts poor prognosis and high tumor immune infiltration in patients with low-grade glioma.
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TYROBP 表达升高预示低级别胶质瘤患者预后不良和肿瘤免疫浸润高
DOI：
10.1186/s12885-021-08456-6
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发表时间：
2021-06-23
期刊：
影响因子：
3.8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Lu J;Peng Y;Huang R;Feng Z;Fan Y;Wang H;Zeng Z;Ji Y;Wang Y;Wang Z
BackgroundTyrosine protein tyrosine kinase binding protein (TYROBP) binds non-covalently to activated receptors on the surface of various immune cells, and mediates signal transduction and cellular activation. It is dysregulated in various malignancies, although little is known regarding its role in low-grade glioma. The aim of this study is to explore the clinicopathological significance, prognostic value and immune signature of TYROBP expression in low-grade glioma (LGG).MethodsThe differentially expressed genes (DEGs) between glioma samples and normal tissues were identified from two GEO microarray datasets using the limma package. The DEGs overlapping across both datasets were functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. STRING database was used to establish the protein-protein interaction (PPI) of the DEGs. The PPI network was visualized by Cytoscape and cytoHubba, and the core module and hub genes were identified. The expression profile of TYROBP and patient survival were validated in the Oncomine, GEPIA2 and CGGA databases. The correlation between TYROBP expression and the clinicopathologic characteristics were evaluated. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed by R based on the LGG data from TCGA. The TIMER2.0 database was used to determine the correlation between TYROBP expression and tumor immune infiltrating cells in the LGG patients. Univariate and multivariate Cox regression analyses were performed to determine the prognostic impact of clinicopathological factors via TCGA database.ResultsSixty-two overlapping DEGs were identified in the 2 datasets, and were mainly enriched in the response to wounding, focal adhesion, GTPase activity and Parkinson disease pathways. TYROBP was identified through the PPI network and cytoHubba. TYROBP expression levels were significantly higher in the LGG tissues compared to the normal tissues, and was associated with worse prognosis and poor clinicopathological parameters. In addition, GSEA showed that TYROBP was positively correlated to neutrophil chemotaxis, macrophage activation, chemokine signaling pathway, JAK-STAT signaling pathway, and negatively associated with gamma aminobutyric acid signaling pathway, neurotransmitter transport, neuroactive ligand receptor intersection etc. TIMER2.0 and ssGSEA showed that TYROBP expression was significantly associated with the infiltration of neutrophils, macrophages, myeloid dendritic cells and monocytes. The infiltration of the M2 phenotype macrophages, cancer-associated fibroblasts and myeloid dendritic cells correlated to worse prognosis in LGG patients. Finally, multivariate analysis showed that elevated TYROBP expression is an independent risk factor for LGG.ConclusionTYROBP is dysregulated in LGG and correlates with immune infiltration. It is a potential therapeutic target and prognostic marker for LGG.
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影响因子：
168.9
作者：
Ricard, Damien;Idbaih, Ahmed;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H
影响因子：
3.4
作者：
Labrakakis, C;Patt, S;Kettenmann, H
通讯作者：
Kettenmann, H
影响因子：
6.2
作者：
Kopatz, Jens;Beutner, Clara;Neumann, Harald
通讯作者：
Neumann, Harald
DOI：
10.4049/jimmunol.1401415
发表时间：
2015-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Spahn JH;Li W;Bribriesco AC;Liu J;Shen H;Ibricevic A;Pan JH;Zinselmeyer BH;Brody SL;Goldstein DR;Krupnick AS;Gelman AE;Miller MJ;Kreisel D
通讯作者：
Kreisel D