Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
- Casalone, E.
- Birolo, G.
- Pardini, B.
- Allione, A.
- Russo, A.
- Catalano, C.
- Mencoboni, M.
- Ferrante, D.
- Magnani, C.
- Sculco, M.
- Dianzani, I.
- Grosso, F.
- Mirabelli, D.
- Filiberti, R. A.
- Rena, O.
- Sacerdote, C.
- Rodriguez-Barranco, M.
- Smith-Byrne, K.
- Panico, S.
- Agnoli, C.
- Johnson, T.
- Kaaks, R.
- Tumino, R.
- Huerta, J. M.
- Riboli, E.
- Heath, A. K.
- Trobajo-Sanmartín, C.
- Schulze, M. B.
- Saieva, C.
- Amiano, P.
- Agudo, A.
- Weiderpass, E.
- Vineis, P.
- Matullo, G.
Keywords
- biomarkers
- early changes
- malignant pleural mesothelioma
- microRNAs
- next generation sequencing
