title: Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers.
abstract: Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bononi
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo-Garofolo"- Trieste, University of Trieste, Trieste, Italy.
authors.forename: Manola
authors.initials: M
authors.lastname: Comar
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Puozzo
authors.affiliation: Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Stendardo
authors.affiliation: Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Boschetto
authors.affiliation: Mesothelioma BioBank, Pathology Unit and City Hospital, Alessandria, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Orecchia
authors.affiliation: Mesothelioma BioBank, Pathology Unit and City Hospital, Alessandria, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Libener
authors.affiliation: Transfusion Medicine, City Hospital, Alessandria, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guaschino
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pietrobon
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.|Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Martini
authors.affiliation: Clinical Unit of Occupational Medicine, Department of Medical Sciences, School of Medicine, University of Trieste, Trieste, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bovenzi
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, School of Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
mesh_terms: D019540:Area Under Curve; D001194:Asbestos / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D000074166:Circulating MicroRNA / Q000097:blood* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008654:Mesothelioma / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects*; D016272:Occupational Health; D020411:Oligonucleotide Array Sequence Analysis; D010997:Pleural Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D000074166:Circulating MicroRNA; C000608605:MIRN1281 microRNA, human; C546085:MIRN197 microRNA, human; C568529:MIRN32 microRNA, human; D035683:MicroRNAs; D001194:Asbestos
keywords: asbestos; biomarker; mesothelioma; microRNA; worker