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Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma
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SYSNO ASEP 0457394 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma Author(s) Santarelli, L. (IT)
Staffolani, S. (IT)
Strafella, E. (IT)
Nocchi, L. (IT)
Manzella, N. (IT)
Grossi, P. (IT)
Bracci, M. (IT)
Pignotti, E. (IT)
Alleva, R. (IT)
Borghi, B. (IT)
Pompili, C. (IT)
Sabbatini, A. (IT)
Rubini, C. (IT)
Zuccatosta, L. (IT)
Bichisecchi, E. (IT)
Valentino, M. (IT)
Horwood, K. (AU)
Comar, M. (IT)
Bovenzi, M. (IT)
Dong, L. F. (AU)
Neužil, Jiří (BTO-N) RID
Amati, M. (IT)
Tomasetti, M. (IT)Source Title Lung Cancer. - : Elsevier - ISSN 0169-5002
Roč. 90, č. 3 (2015), s. 457-464Number of pages 8 s. Language eng - English Country IE - Ireland Keywords Mesothelioma ; Lung cancer ; Mesothelin ; BREAST-CANCER METASTASIS Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP301/10/1937 GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 UT WOS 000366873700013 DOI 10.1016/j.lungcan.2015.09.021 Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2016
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