Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study

Cancers 2022 December 25 [Link]

Elisabetta Casalone, Giovanni Birolo, Barbara Pardini, Alessandra Allione, Alessia Russo, Chiara Catalano, Manlio Mencoboni, Daniela Ferrante, Corrado Magnani, Marika Sculco, Irma Dianzani, Federica Grosso, Dario Mirabelli, Rosa Angela Filiberti, Ottavio Rena, Carlotta Sacerdote, Miguel Rodriguez-Barranco, Karl Smith-Byrne, Salvatore Panico, Claudia Agnoli, Theron Johnson, Rudolf Kaaks, Rosario Tumino, José María Huerta, Elio Riboli, Alicia K Heath, Camino Trobajo-Sanmartín, Matthias B Schulze, Calogero Saieva, Pilar Amiano, Antonio Agudo, Elisabete Weiderpass, Paolo Vineis, Giuseppe Matullo


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.