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High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma.

ABSTRACT: AIMS:To evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis. METHODS:Oncomine, GEO, and The Cancer Genome Atlas databases were used to examine the COPB2 transcript levels in glioma tissues. Gene expression profiles with clinical information from low-grade glioma and glioblastoma (GBM) projects were analyzed for associations between COPB2 expression and clinicopathologic characteristics. Kaplan-Meier survival and Cox regression analyses were used for survival analysis. Gene set enrichment analysis (GSEA) was conducted to screen the pathways involved in COPB2 expression. Gene set variation analysis (GSVA) and correlograms were performed to verify the correlations between COPB2 and inflammatory responses. Canonical correlation analyses examined whether COPB2-high patients have more infiltrating inflammatory and immune cells. RESULTS:COPB2 was highly expressed in gliomas and high COPB2 expression correlated with shorter overall survival time and several poor clinical prognostic variables. GSEA indicated that some immune-related pathways and other signaling pathways in cancer were associated with the COPB2-high phenotype. The GSVA and canonical correlation analysis demonstrated that COPB2 expression was closely linked to inflammatory and immune responses, and higher immune cell infiltration. CONCLUSIONS:COPB2 may be a potential prognostic biomarker and an immunotherapeutic target for glioma.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC7081167 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma.

Zhou Yan Y Wang Xuan X Huang Xing X Li Xu-Dong XD Cheng Kai K Yu Hao H Zhou Yu-Jie YJ Lv Peng P Jiang Xiao-Bing XB

CNS neuroscience & therapeutics 20191111 3

<h4>Aims</h4>To evaluate the clinical significance of coatomer protein complex subunit beta 2 (COPB2) in patients with glioma using a bioinformatics analysis.<h4>Methods</h4>Oncomine, GEO, and The Cancer Genome Atlas databases were used to examine the COPB2 transcript levels in glioma tissues. Gene expression profiles with clinical information from low-grade glioma and glioblastoma (GBM) projects were analyzed for associations between COPB2 expression and clinicopathologic characteristics. Kapla ...[more]

PMID: 31710183

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Project description:Background: Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR. Results: HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue (p < 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169-2.266, p = 0.004) and GSE41613 data (HR = 2.238, p = 0.013). The methylation level of HMMR negatively correlated with the HMMR expression (R = -0.12, p < 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation (p < 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed that HMMR expression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288, p = 0.045) and progression-free survival (HR = 2.247, p = 0.038) in 70 HNSCC. Conclusions: This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.

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High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma.

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High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma.

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