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pmid:35865015
Identification of BST2 Contributing to the Development of Glioblastoma Based on Bioinformatics Analysis.
Yang Kong · Zhiwei Xue · Haiying Wang · Guangqiang Cui · Anjing Chen · Jie Liu · Jian Wang · Xingang Li · Bin Huang
Frontiers in genetics · 2022 doi:10.3389/fgene.2022.890174
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Experiment
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Complete file
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However, in human glioblastoma multiforme (GBM) which develops in part by attracting immune cell types intrinsic to the human brain (microglia), standard immunotherapy has yielded inconsistent results in experimental models and patients. Here, we analyzed publicly available expression datasets to identify molecules possibly associated with immune response originating from or influencing the tumor microenvironment in primary tumor samples. Using three glioma datasets (GSE16011, Rembrandt-glioma and TCGA-glioma), we first analyzed the data to distinguish between GBMs of high and low tumor cell purity, a reflection of the cellular composition of the tumor microenvironment, and second, to identify differentially expressed genes (DEGs) between these two groups using GSEA and other analyses. Tumor purity was negatively correlated with patient prognosis. The interferon gamma-related gene BST2 emerged as a DEG that was highly expressed in GBM and negatively correlated with tumor purity. BST2 high tumors also tended to harbor PTEN mutations (31 vs. 9%, BST2 high versus BST2 low ) while BST2 low tumors more often had sustained TP53 mutations (8 versus 36%, BST2 high versus BST2 low ). Prognosis of patients with BST2 high tumors was also poor relative to patients with BST2 low tumors. Further molecular in silico analysis demonstrated that high expression of BST2 was negatively correlated with CD8+ T cells but positively correlated with macrophages with an M2 phenotype. Further functional analysis demonstrated that BST2 was associated with multiple immune checkpoints and cytokines, and may promote tumorigenesis and progression through interferon gamma, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling and the TNF-α signaling via NF-kB pathway. Finally, a series of experiments confirmed that the expression of BST2 can be significantly increased by IFN induction, and knockdown of BST2 can significantly inhibit the growth and invasion of GBM cells, and may affect the phenotype of tumor-associated macrophages. In conclusion, BST2 may promote the progression of GBM and may be a target for treatment.", "claims": [{"id": "claim-method", "statement": "Using Kaplan-Meier analysis, we examined overall survival of patients in the TCGA-GBM dataset based on high and low expression of BST2, IFI44, LGALS3BP, LY6E, NOD1, USP18, OAS3, and PARP12 in tumors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35865015", "locator": "sections[18] \"High Expression of BST2 is Associated With Worse Prognosis\" paragraph 2", "quote": "Using Kaplan-Meier analysis, we examined overall survival of patients in the TCGA-GBM dataset based on high and low expression of BST2, IFI44, LGALS3BP, LY6E, NOD1, USP18, OAS3, and PARP12 in tumors."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35865015", "locator": "sections[28] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Tumor purity was negatively correlated with patient prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35865015", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Tumor purity was negatively correlated with patient prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Tumor purity was negatively correlated with patient prognosis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35865015"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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