title: Examination of Epigenetic and other Molecular Factors Associated with mda-9/Syntenin Dysregulation in Cancer Through Integrated Analyses of Public Genomic Datasets.
abstract: mda-9/Syntenin (melanoma differentiation-associated gene 9) is a PDZ domain containing, cancer invasion-related protein. 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.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Manny D
authors.initials: MD
authors.lastname: Bacolod
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Swadesh K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Upneet K
authors.initials: UK
authors.lastname: Sokhi
authors.affiliation: VCU Bioinformatics Program, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Bradley
authors.affiliation: VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; Department of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Fenstermacher
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA. Electronic address: pbfisher@vcu.edu.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D030541:Databases, Genetic; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D015398:Signal Transduction / Q000235:genetics; D053676:Syntenins / Q000235:genetics*
chemical_list: C109621:SDCBP protein, human; D053676:Syntenins
keywords: ENCODE; Epigenetics; GEO; Glioma; MDA-9; Melanoma; SDCBP; Syntenin; TCGA; VIGOR