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Downregulation of LUZP2 Is Correlated with Poor Prognosis of Low-Grade Glioma.

ABSTRACT: Background:LUZP2 is a protein limitedly expressed in the brain and spinal cord, while there are few studies on it in brain tumors. Low-grade glioma (LGG) is one of the most common brain tumors. However, the biological behavior of LGG is not very clear at present. This study was aimed at exploring the role of LUZP2 in LGG. Methods:By data mining in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), the expression, clinical characteristics, and potential regulatory mechanism of LUZP2 in LGG were assessed. The regulatory miRNAs of LUZP2 were predicted using miRDB, TargetScan, and miRTarBase. Meanwhile, the potential biological function of coexpressed genes was investigated by GO and KEGG analyses. Results:LUZP2 expression was downregulated with the increase of tumor grade (p < 0.05). Low LUZP2 expression independently predicted poor OS in LGG in TCGA cohort and the CGGA part B and part C cohorts (all p < 0.001). Additionally, LUZP2 was targeted by miR-142-5p according to 2 prediction databases and 1 validated database, which was negatively related to LUZP2 mRNA expression (p < 0.001). Kaplan-Meier analyses demonstrated that low miR-142-5p expression was significantly associated with poor OS (p < 0.001). Furthermore, coexpression genes of LUZP2 were significantly involved in nervous system development and metabolic pathways. Conclusions:LUZP2 may be crucial for nervous system extracellular matrix development and serve as an important clinical biomarker for LGG patients. miR-142-5p upregulation could be the upstream regulator that contributed to LUZP2 downregulation.

SUBMITTER: Li Y

PROVIDER: S-EPMC7368956 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Downregulation of LUZP2 Is Correlated with Poor Prognosis of Low-Grade Glioma.

Li Yong Y Deng Gang G Qi Yangzhi Y Zhang Huikai H Jiang Hongxiang H Geng Rongxin R Ye Zhang Z Liu Baohui B Chen Qianxue Q

BioMed research international 20200709

<h4>Background</h4>LUZP2 is a protein limitedly expressed in the brain and spinal cord, while there are few studies on it in brain tumors. Low-grade glioma (LGG) is one of the most common brain tumors. However, the biological behavior of LGG is not very clear at present. This study was aimed at exploring the role of LUZP2 in LGG.<h4>Methods</h4>By data mining in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), the expression, clinical characteristics, and potential regulato ...[more]

PMID: 32695826

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Project description: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.

Dataset Information

Downregulation of LUZP2 Is Correlated with Poor Prognosis of Low-Grade Glioma.

Publications

Downregulation of LUZP2 Is Correlated with Poor Prognosis of Low-Grade Glioma.

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