A four-miRNA signature as a potential biomarker of malignant mesothelioma patients from hand-spinning asbestos exposed area in Eastern China

Malignant mesothelioma (MM) is an aggressive malignant tumor of mesothelial origin that develops mainly in the parietal pleura or peritoneum and is strongly associated with asbestos exposure. MicroRNAs (miRNAs) can serve as biomarkers for the in vitro diagnosis of tumors. To investigate the differential expression of miRNAs in MM patients and identify potential diagnostic biomarkers, we sequenced miRNAs in formalin-fixed paraffin-embedded (FFPE) tumor tissues from 85 malignant pleural mesothelioma patients (samples collected between 1998 and 2017), and compared them with adjacent normal tissues, and the expression of four miRNAs was validated using in situ hybridization. Moreover, the expression differences of these four miRNAs in the plasma were also compared between lung cancer (LC) patients, patients with pleural plaques (PP), asbestos-exposed (AE) subjects and healthy controls (196 plasma samples collected from this handing-spun asbestos-exposed area) by qPCR. We found a total of 31 differentially expressed miRNAs in the tumor tissue of mesothelioma patients compared with the adjacent normal tissue, with 18 upregulated miRNAs and 13 downregulated miRNAs. The elevated expression of miR-19b, miR-26a, miR-26b, and miR-29a in FFPE tumor tissue was further validated in both the cytoplasm and the nucleus using fluorescence in situ hybridization (FISH). Furthermore, the plasma expression levels of miR-19b and miR-29a in the mesothelioma group were significantly higher than those in any of the other four groups, and similar expression differences were found in miR-26a and miR-26b between the mesothelioma group and any other group except the LC group. Diagnostic value analysis indicated high sensitivity and specificity of these four miRNAs in distinguishing MM patients from PP patients, AE subjects, and healthy controls. Conclusively, miR-19b, miR-26a, miR-26b and miR-29a are potential blood biomarkers for the early or differential diagnosis of MM.