• Morten Andersen, Davide Trapani, Jesper Ravn, Jens Benn Sørensen, Andersen Claus Bøgelund CB Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Morten Grauslund, and Eric Santoni-Rugiu.
• Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
• Anticancer Res. 2015 Nov 1; 35 (11): 6223-9.

Background/AimWe recently reported that miR-126 is down-regulated in malignant pleural mesothelioma (MPM) and can be combined into a 4-microRNA-classifier that can accurately diagnose MPM with high sensitivity and specificity. Herein we analyzed the epigenetic regulation of miR-126 and its host gene EGF-like domain, multiple 7 (EGFL7).Materials And MethodsResected formalin-fixed paraffin-embedded MPM tissues from 29 patients, 14 patient-matched non-neoplastic pleura (NNP) specimens, 5 MPM diagnostic biopsies (DB), and 5 samples of pneumothorax-induced benign reactive mesothelial proliferation (PTHX) were analyzed. miR-126 and EGFL7 mRNA were quantified by RT-qPCR. CpG-islands' methylation in the EGFL7 promoter was analyzed using methylation-specific PCR and in the MIR126-containing intron 7 was quantified by pyrosequencing.ResultsRelative to NNP, EGFL7 was under-expressed more than 4-fold in MPM (p<0.001). EGFL7 mRNA and miR-126 levels correlated in MPM (p<0.01) and NNP (p<0.001). The EGFL7 promoter region was hypermethylated in 69% of MPM and 80% of DB samples, but not in NNP and PTHX samples. EGFL7 promoter hypermethylation was associated with epithelioid histology (p<0.05) and reduced patient-survival (p<0.05).ConclusionIn MPM, DNA-hypermethylation down-regulates miR-126 and its host gene EGFL7, therefore is a poor prognostic factor, and may represent a future therapeutic target for de-methylating strategies re-establishing EGFL7 and miR-126 expression.Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

44 keywords...

hide…