Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets.

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In this study, we employed multiple integrated bioinformatic approaches to identify the probable epigenetic factors, molecular pathways, and functionalities associated with mda-9 dysregulation during cancer progression. Analyses of publicly available genomic data (e.g., expression, copy number, methylation) from TCGA, GEO, ENCODE, and Human Protein Atlas projects led to the following observations: (a) mda-9 expression correlates with both copy number and methylation level of an intronic CpG site (cg1719774) located downstream of the CpG island, (b) cg1719774 methylation is a likely prognostic marker in glioma, (c) among 22 cancer types, melanoma exhibits the highest mda-9 level, and lowest level of methylation at cg1719774, (d) cg1719774 hypomethylation is also associated with histone modifications (at the mda-9 locus) indicative of more active transcription, (e) using Gene Set Enrichment Analysis (GSEA), and the Virtual Gene Overexpression or Repression (VIGOR) analytical scheme, we were able to predict mda-9's association with extracellular matrix organization (e.g., MMPs, collagen, integrins), IGFBP2 and NF-κB signaling pathways, phospholipid metabolism, cytokines (e.g., interleukins), CTLA-4, and components of complement cascade pathways. Indeed, previous publications have shown that many of the aforementioned genes and pathways are associated with mda-9's functionality.", "claims": [{"id": "claim-target-result", "statement": "The paper used integrated bioinformatic analyses of public genomic data from TCGA, GEO, ENCODE, and the Human Protein Atlas, combining GSEA with the VIGOR scheme, and identified epigenetic factors and pathways associated with mda-9 dysregulation, including cg17197774 methylation, histone modifications, extracellular matrix organization, IGFBP2 and NF-κB signaling, phospholipid metabolism, cytokines, CTLA-4, and complement cascade pathways.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26093898", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this study, we employed multiple integrated bioinformatic approaches to identify the probable epigenetic factors, molecular pathways, and functionalities associated with mda-9 dysregulation during cancer progression."}, {"asset": "source:pmid:26093898", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Analyses of publicly available genomic data (e.g., expression, copy number, methylation) from TCGA, GEO, ENCODE, and Human Protein Atlas projects led to the following observations:"}, {"asset": "source:pmid:26093898", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using Gene Set Enrichment Analysis (GSEA), and the VIGOR (Virtual Gene Over-expression or Repression ) analytical scheme, we were able to predict mda-9’s association with extracellular matrix organization (e.g., MMPs, collagen, integrins), IGFBP2 and NF-κB signaling pathways, phospholipid metabolism, cytokines (e.g., interleukins), CTLA-4, and components of complement cascade pathways."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used integrated bioinformatic analyses of public genomic data from TCGA, GEO, ENCODE, and the Human Protein Atlas, combining GSEA with the VIGOR scheme, and identified epigenetic factors and pathways associated with mda-9 dysregulation, including cg17197774 methylation, histone modifications, extracellular matrix organization, IGFBP2 and NF-κB signaling, phospholipid metabolism, cytokines, CTLA-4, and complement cascade pathways.", "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:26093898"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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