TY - JOUR

T1 - Transcriptomic analysis of the claudin interactome in malignant pleural mesothelioma

T2 - Evaluation of the effect of disease phenotype, asbestos exposure, and CDKN2A deletion status

AU - Rouka, Erasmia

AU - Vavougios, Georgios D.

AU - Solenov, Evgeniy I.

AU - Gourgoulianis, Konstantinos I.

AU - Hatzoglou, Chrissi

AU - Zarogiannis, Sotirios G.

PY - 2017/3/21

Y1 - 2017/3/21

N2 - 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 which CLAUDIN (CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressed CLDN genes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure, CDKN2A deletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studied CLDNs (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-15 is significantly under-expressed in the cohort of patients with previous history of asbestos exposure. CLDN-15 was also found significantly underexpressed in patients lacking the CDKN2A gene. These results warrant the detailed in vitro investigation of the role of CDLN-15 in the pathobiology of MPM.

AB - 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 which CLAUDIN (CLDN) genes are differentially expressed in MPM as compared to controls. Using the same approach we identified the interactome of the differentially expressed CLDN genes and assessed their expression profile. Subsequently, we evaluated the effect of tumor histology, asbestos exposure, CDKN2A deletion status, and gender on the gene expression level of the claudin interactome. We found that 5 out of 15 studied CLDNs (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-15 is significantly under-expressed in the cohort of patients with previous history of asbestos exposure. CLDN-15 was also found significantly underexpressed in patients lacking the CDKN2A gene. These results warrant the detailed in vitro investigation of the role of CDLN-15 in the pathobiology of MPM.

KW - Asbestos

KW - CDKN2A

KW - Claudins

KW - Interactome

KW - Malignant mesothelioma

KW - Pleura

KW - Tight junctions

KW - Transcriptome

KW - asbestos

KW - transcriptome

KW - CANCER

KW - TIGHT JUNCTIONS

KW - LUNG-DISEASES

KW - MOLECULAR PATHOGENESIS

KW - pleura

KW - tight junctions

KW - DIFFERENTIAL-DIAGNOSIS

KW - malignant mesothelioma

KW - ADENOCARCINOMA

KW - OVARIAN/PERITONEAL SEROUS CARCINOMA

KW - EPITHELIAL-CELLS

KW - VE-CADHERIN

KW - interactome

KW - claudins

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=85016146774&partnerID=8YFLogxK

U2 - 10.3389/fphys.2017.00156

DO - 10.3389/fphys.2017.00156

M3 - Article

C2 - 28377727

AN - SCOPUS:85016146774

VL - 8

SP - 156

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - MAR

M1 - 156

ER -