title: Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143, miR-145, and miR-652 were significantly down-regulated (≥twofold) in resected MPM and/or chemotherapy-naïve diagnostic tumor biopsy samples. The miRNA expression pattern was validated by RT-qPCR in a cohort of 40 independent MPMs. By performing binary logistic regression on the RT-qPCR data for the four miRNAs, the established four-miRNA classifier differentiated MPM from NNP with high sensitivity and specificity (area under the curve, 0.96; 95% CI, 0.92-1.00). The classifier's optimal logit(P) value of 0.62 separated NNP and MPM samples with a sensitivity of 0.95 (95% CI, 0.89-1.00), a specificity of 0.93 (95% CI, 0.87-0.99), and an overall accuracy of 0.94 (95% CI, 0.88-1.00). The level of miR-126 in MPM was inversely correlated with that of the known target, the large neutral amino acid transporter, small subunit 1 (r = -0.38; 95% CI, -0.63 to -0.06). Overall, these results indicate that these four miRNAs may be suitable biomarkers for distinguishing MPM from RMPs.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: morten.andersen@regionh.dk.
authors.forename: Morten
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Grauslund
authors.affiliation: Department of Thoracic Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ravn
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jens B
authors.initials: JB
authors.lastname: Sørensen
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: eric.santoni-rugiu.02@regionh.dk.
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
mesh_terms: D000368:Aged; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D010994:Pleura / Q000378:metabolism / Q000473:pathology; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods
chemical_list: C527111:MIRN126 microRNA, human; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; C574011:MIRN652 microRNA, human; D035683:MicroRNAs