MicroRNAs In Blood As Biomarker Of Pleural Malignant Mesothelioma

Valentina BOLLATI, Università degli Studi di Milano, Italy
CAVALLERI T. 2 , FAVERO C. 1 , DIONI L. 1 , MENSI C. 3 , BAREGGI C. 4 , BORDINI L. 3 , PALLESCHI A. 5 , ALDO T. 1 , CONSONNI D. 3 , PESATORI A. 1,3

1 EPIGET, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
2 Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Italy
3 Department of Preventive Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
4 Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
5 Thoracic Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

Purpose: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer refractory to current therapies caused almost exclusively by asbestos. New specific diagnostic markers for early MPM diagnosis are needed. MiRNAs are single stranded noncoding that post-transcriptionally regulate gene expression by triggering mRNA cleavage or repressing translation. Changes in the expression of miRNAs have been implicated in several diseases and cancers, including MPM. miRNAs are stable molecules that can be easily investigated in different specimens (e.g. blood), and used as a disease biomarker. Our aim was to determine if a specific miRNA signature in plasma may help to discriminate between malignant pleural mesothelioma patients (MPM) and healthy subjects with a Past Asbestos Exposure (PAE).
Methods: We investigated a group of 23 MPM patients and 19 healthy subjects with Past Asbestos Exposure (PAE). In this study population we screened 754 miRNAs in blood by TaqMan™ OpenArray® Human MiRNA Panel. Than we selected for validation, in the same groups of subjects, the top-23 differential miRNAs. RNU48 was used as endogenous control. We used multiple linear and logistic regression models adjusted for age, sex, BMI, and smoking habits to compare miRNAs profiling between MPM and PAE subjects.
Results: After miRNA screening, we identified 29 differential miRNAs in plasma. Among the top 23 differential miRNAs, 19 were validated by Real time PCR and were able to discriminate between MPM and PEA subjects. In receiver operating characteristic (ROC) curve analysis, the three best miRNAs were miR-103 (area under curve, AUC=0.82), miR-98 (AUC=0.82) and miR-744 (AUC=0.81).
Conclusions: The identified signature was useful for MPM diagnosis. Further studies are needed to verify if they can be of help for early MPM diagnosis and/or to detect high risk groups.
Funding source: Lombardy Region; Ministry of Health and INAIL; Associazione Italiana per la Ricerca sul Cancro.