Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma
American Journal of Physiology: Lung Cellular and Molecular Physiology 2015 August 7 [Epub ahead of print] [Link]
Vavougios GD, Solenov EI, Hatzoglou C, Baturina GS, Katkova LE, Molyvdas PA, Gourgoulianis KI, Zarogiannis SG.
Abstract
The aim of our study was to assess the differential gene expression of PARK7 interactome in MPM using data mining techniques in order to identify novel candidate genes that may play a role in the pathogenicity of malignant pleural mesothelioma (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, STUB1 were significantly over- whereas TRAF6 and MTA2 were significantly under-expressed 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 versus 8.7 months of those that had low expression. For validation purposes we performed a meta-analysis in Oncomine database in 5 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.
