TY - JOUR T1 - Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies. JF - Cancer Epidemiol Biomarkers Prev Y1 - 2019 A1 - Santarelli, Lory A1 - Gaetani, Simona A1 - Monaco, Federica A1 - Bracci, Massimo A1 - Valentino, Matteo A1 - Amati, Monica A1 - Rubini, Corrado A1 - Sabbatini, Armando A1 - Pasquini, Ernesto A1 - Zanotta, Nunzia A1 - Comar, Manola A1 - Neuzil, Jiri A1 - Tomasetti, Marco A1 - Bovenzi, Massimo AB -

BACKGROUND: Altered miRNA expression is an early event upon exposure to occupational/environmental carcinogens; thus, identification of a novel asbestos-related profile of miRNAs able to distinguish asbestos-induced cancer from cancer with different etiology can be useful for diagnosis. We therefore performed a study to identify miRNAs associated with asbestos-induced malignancies.

METHODS: Four groups of patients were included in the study, including patients with asbestos-related (NSCLC) and asbestos-unrelated non-small cell lung cancer (NSCLC) or with malignant pleural mesothelioma (MPM), and disease-free subjects (CTRL). The selected miRNAs were evaluated in asbestos-exposed population.

RESULTS: Four serum miRNAs, that is miR-126, miR-205, miR-222, and miR-520g, were found to be implicated in asbestos-related malignant diseases. Notably, increased expression of miR-126 and miR-222 were found in asbestos-exposed subjects, and both miRNAs are involved in major pathways linked to cancer development. Epigenetic changes and cancer-stroma cross-talk could induce repression of miR-126 to facilitate tumor formation, angiogenesis, and invasion.

CONCLUSIONS: This study indicates that miRNAs are potentially involved in asbestos-related malignancies, and their expression outlines mechanism(s) whereby miRNAs may be involved in an asbestos-induced pathogenesis.

IMPACT: The discovery of a miRNA panel for asbestos-related malignancies would impact on occupational compensation and may be utilized for screening asbestos-exposed populations.

VL - 28 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30257964?dopt=Abstract ER - TY - JOUR T1 - Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma. JF - Lung Cancer Y1 - 2015 A1 - Santarelli, Lory A1 - Staffolani, Sara A1 - Strafella, Elisabetta A1 - Nocchi, Linda A1 - Manzella, Nicola A1 - Grossi, Paola A1 - Bracci, Massimo A1 - Pignotti, Elettra A1 - Alleva, Renata A1 - Borghi, Battista A1 - Pompili, Cecilia A1 - Sabbatini, Armando A1 - Rubini, Corrado A1 - Zuccatosta, Lina A1 - Bichisecchi, Elisabetta A1 - Valentino, Matteo A1 - Horwood, Keith A1 - Comar, Manola A1 - Bovenzi, Massimo A1 - Dong, Lan-Feng A1 - Neuzil, Jiri A1 - Amati, Monica A1 - Tomasetti, Marco AB -

OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage.

MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated.

RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/26431916?dopt=Abstract ER -