title: Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma.
abstract: The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients (network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease.
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece;
authors.forename: Georgios D
authors.initials: GD
authors.lastname: Vavougios
authors.affiliation: Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Novosibirsk State University, Novosibirsk, Russia; and.
authors.forename: Evgeniy I
authors.initials: EI
authors.lastname: Solenov
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece; Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.
authors.forename: Chrissi
authors.initials: C
authors.lastname: Hatzoglou
authors.affiliation: Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia;
authors.forename: Galina S
authors.initials: GS
authors.lastname: Baturina
authors.affiliation: Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia;
authors.forename: Liubov E
authors.initials: LE
authors.lastname: Katkova
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.
authors.forename: Paschalis Adam
authors.initials: PA
authors.lastname: Molyvdas
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece;
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.affiliation: Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece; Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece szarog@med.uth.gr.
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Zarogiannis
mesh_terms: D019295:Computational Biology / Q000379:methods; D057225:Data Mining / Q000379:methods; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000071617:Protein Deglycase DJ-1; D015996:Survival Rate
chemical_list: C464790:Bbs1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
keywords: BBS1; NuRD; PARK7; computational transcriptomics; malignant pleural mesothelioma