%0 Journal Article %J Lung Cancer %D 2015 %T Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma. %A Santarelli, Lory %A Staffolani, Sara %A Strafella, Elisabetta %A Nocchi, Linda %A Manzella, Nicola %A Grossi, Paola %A Bracci, Massimo %A Pignotti, Elettra %A Alleva, Renata %A Borghi, Battista %A Pompili, Cecilia %A Sabbatini, Armando %A Rubini, Corrado %A Zuccatosta, Lina %A Bichisecchi, Elisabetta %A Valentino, Matteo %A Horwood, Keith %A Comar, Manola %A Bovenzi, Massimo %A Dong, Lan-Feng %A Neuzil, Jiri %A Amati, Monica %A Tomasetti, Marco %X

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.

%B Lung Cancer %8 2015 Sep 25 %G ENG %1 http://www.ncbi.nlm.nih.gov/pubmed/26431916?dopt=Abstract %R 10.1016/j.lungcan.2015.09.021