Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma

Am J Physiol Lung Cell Mol Physiol. 2015 Oct 1;309(7):L677-86. doi: 10.1152/ajplung.00051.2015. Epub 2015 Aug 7.

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.

Keywords: BBS1; NuRD; PARK7; computational transcriptomics; malignant pleural mesothelioma.

MeSH terms

  • Computational Biology / methods
  • Data Mining / methods
  • Databases, Genetic*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • Intracellular Signaling Peptides and Proteins* / genetics
  • Intracellular Signaling Peptides and Proteins* / metabolism
  • Male
  • Mesothelioma* / genetics
  • Mesothelioma* / metabolism
  • Mesothelioma* / mortality
  • Microtubule-Associated Proteins* / biosynthesis
  • Microtubule-Associated Proteins* / genetics
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Oncogene Proteins* / genetics
  • Oncogene Proteins* / metabolism
  • Pleural Neoplasms* / genetics
  • Pleural Neoplasms* / metabolism
  • Pleural Neoplasms* / mortality
  • Protein Deglycase DJ-1
  • Survival Rate

Substances

  • Bbs1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Oncogene Proteins
  • PARK7 protein, human
  • Protein Deglycase DJ-1