GRN is a prognostic biomarker and correlated with immune infiltration in glioma: A study based on TCGA data

Frontiers in Oncology

Oncology

You-Jie Zeng¹  Tao Song²  Zhong-Xu Hu²  You-Xuan Wu³  Xue-Feng Zhong³  Hai-Yan Xiao⁴  Su-Mei Xu⁴  Dai Li⁴ 

[1] Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China;Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha, China;Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China;

关键词: GRN;    glioblastoma;    biomarker;    immune infiltration;    prognosis;    RNA-seq;    bioinformatics analysis;    prognostic signature;   

DOI  :  10.3389/fonc.2023.1162983

 received in 2023-02-10, accepted in 2023-03-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundAmong primary brain tumors, gliomas are associated with a poor prognosis and a median survival that varies depending on the tumor grade and subtype. As the most malignant form of glioma, glioblastoma (GBM) constitutes a significant health concern. Alteration in granulin(GRN) has been proved to be accountable for several diseases. However, the relationship between GRN and GBM remains unclear. We evaluated the role of GRN in GBM through The Cancer Genome Atlas (TCGA) databaseMethodsFirst, we assessed the relationship between GRN and GBM through the GEPIA database. Next, the relationship between GRN and GBM prognosis was analyzed by logistic regression and multivariate cox methods. Using CIBERSORT and the GEPIA correlation module, we also investigated the link between GRN and immune infiltrates in cancer. Using the TCGA data, a gene set enrichment analysis (GSEA) was performed. We also employed Tumor Immune Estimation Resource (TIMER) to examine the data set of GRN expression and immune infiltration level in GBM and investigate the cumulative survival in GBM. We also validated tissues from GBM patients by Western blotting, RT-qPCR, and immunohistochemistry.ResultsIncreased GRN expression was shown to have a significant relationship to tumor grade in a univariate study utilizing logistic regression. Furthermore, multivariate analysis disclosed that GRN expression down-regulation is an independent predictive factor for a favorable outcome. GRN expression level positively correlates with the number of CD4+ T cells, neutrophils, macrophages, and dendritic cells (DCs) that infiltrate a GBM. The GSEA also found that the high GRN expression phenotype pathway was enriched for genes involved in immune response molecular mediator production, lymphocyte-mediated immunity, cytokine-mediated signaling pathway, leukocyte proliferation, cell chemotaxis, and CD4+ alpha beta T cell activation. Differentially enriched pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) include lysosome, apoptosis, primary immunodeficiency, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and B cell receptor signaling pathway. Validated result showed that GRN was upregulated in GBM tissues. These results suggested that GRN was a potential indicator for the status of GBM.ConclusionGRN is a prognostic biomarker and correlated with immune infiltrates in GBM.

【 授权许可】

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Copyright © 2023 Xu, Xiao, Hu, Zhong, Zeng, Wu, Li and Song