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  • Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma

    Author(s)
    Santarelli, Lory
    Staffolani, Sara
    Strafella, Elisabetta
    Nocchi, Linda
    Manzella, Nicola
    Grossi, Paola
    Bracci, Massimo
    Pignotti, Elettra
    Alleva, Renata
    Borghi, Battista
    Pompili, Cecilia
    Sabbatini, Armando
    Rubini, Corrado
    Zuccatosta, Lina
    Bichisecchi, Elisabetta
    Valentino, Matteo
    Horwood, Keith
    Comar, Manola
    Bovenzi, Massimo
    Dong, Lan-Feng
    Neuzil, Jiri
    Amati, Monica
    Tomasetti, Marco
    Griffith University Author(s)
    Neuzil, Jiri
    Dong, Lan-feng
    Year published
    2015
    Metadata
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    Abstract
    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 ...
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    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.
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    Journal Title
    Lung Cancer
    Volume
    90
    Issue
    3
    DOI
    https://doi.org/10.1016/j.lungcan.2015.09.021
    Subject
    Clinical sciences
    Clinical sciences not elsewhere classified
    Oncology and carcinogenesis
    Oncology and carcinogenesis not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/101713
    Collection
    • Journal articles

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