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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.

frontiers in physiology

Transcriptomic Analysis of the Claudin Interactome in Malignant Pleural Mesothelioma: Evaluation of the Effect of Disease Phenotype, Asbestos Exposure, and CDKN2A Deletion Status