Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma

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.