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

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    0457394 - BTO-N 2016 RIV IE eng J - Článek v odborném periodiku
    Santarelli, L. - Staffolani, S. - Strafella, E. - Nocchi, L. - Manzella, N. - Grossi, P. - Bracci, M. - Pignotti, E. - Alleva, R. - Borghi, B. - Pompili, C. - Sabbatini, A. - Rubini, C. - Zuccatosta, L. - Bichisecchi, E. - Valentino, M. - Horwood, K. - Comar, M. - Bovenzi, M. - Dong, L. F. - Neužil, Jiří - Amati, M. - Tomasetti, M.
    Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma.
    Lung Cancer. Roč. 90, č. 3 (2015), s. 457-464. ISSN 0169-5002
    Grant CEP: GA ČR(CZ) GAP301/10/1937; GA MŠk(CZ) ED1.1.00/02.0109
    Institucionální podpora: RVO:86652036
    Klíčová slova: Mesothelioma * Lung cancer * Mesothelin * BREAST-CANCER METASTASIS
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Impakt faktor: 3.767, rok: 2015

    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, miR126, 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. (c) 2015 Elsevier Ireland Ltd. All rights reserved.
    Trvalý link: http://hdl.handle.net/11104/0257794