title: Transcriptomic Analysis of the Claudin Interactome in Malignant Pleural Mesothelioma: Evaluation of the Effect of Disease Phenotype, Asbestos Exposure, and CDKN2A Deletion Status.
abstract: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor primarily associated with asbestos exposure. Early detection of MPM is restricted by the long latency period until clinical presentation, the ineffectiveness of imaging techniques in early stage detection and the lack of non-invasive biomarkers with high sensitivity and specificity. In this study we used transcriptome data mining in order to determine whichCLAUDIN(CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressedCLDNgenes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure,CDKN2Adeletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studiedCLDNs(4, 5, 8, 10, 15) and 4 out of 27 available interactors (S100B, SHBG, CDH5, CXCL8) were differentially expressed in MPM specimens vs. healthy tissues. The genes encoding the CLDN-15 and S100B proteins present differences in their expression profile between the three histological subtypes of MPM. Moreover,CLDN-15is significantly under-expressed in the cohort of patients with previous history of asbestos exposure.CLDN-15was also found significantly underexpressed in patients lacking theCDKN2Agene. These results warrant the detailedin vitroinvestigation of the role of CDLN-15 in the pathobiology of MPM.
authors.affiliation: Gradute Program in Primary Health Care, Faculty of Medicine, University of Thessaly Larissa, Greece.
authors.forename: Erasmia
authors.initials: E
authors.lastname: Rouka
authors.affiliation: Department of Respiratory Medicine, University of Thessaly Medical School 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 SciencesNovosibirsk, Russia; Department of Physiology, Novosibirsk State UniversityNovosibirsk, Russia.
authors.forename: Evgeniy I
authors.initials: EI
authors.lastname: Solenov
authors.affiliation: Gradute Program in Primary Health Care, Faculty of Medicine, University of ThessalyLarissa, Greece; Department of Respiratory Medicine, University of Thessaly Medical SchoolLarissa, Greece.
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.affiliation: Gradute Program in Primary Health Care, Faculty of Medicine, University of ThessalyLarissa, Greece; Department of Respiratory Medicine, University of Thessaly Medical SchoolLarissa, Greece; Department of Physiology, Faculty of Medicine, University of ThessalyLarissa, Greece.
authors.forename: Chrissi
authors.initials: C
authors.lastname: Hatzoglou
authors.affiliation: Gradute Program in Primary Health Care, Faculty of Medicine, University of ThessalyLarissa, Greece; Department of Respiratory Medicine, University of Thessaly Medical SchoolLarissa, Greece; Department of Physiology, Faculty of Medicine, University of ThessalyLarissa, Greece.
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Zarogiannis
keywords: CDKN2A; asbestos; claudins; interactome; malignant mesothelioma; pleura; tight junctions; transcriptome