Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma
| Autor: | Armando Sabbatini, Linda Nocchi, Elisabetta Strafella, Monica Amati, Jiri Neuzil, Matteo Valentino, Keith Horwood, Renata Alleva, Battista Borghi, Corrado Rubini, Manola Comar, Paola Grossi, Lina Zuccatosta, Cecilia Pompili, Nicola Manzella, Elisabetta Bichisecchi, Massimo Bovenzi, Elettra Pignotti, Sara Staffolani, Massimo Bracci, Lory Santarelli, Lan-Feng Dong, Marco Tomasetti |
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| Přispěvatelé: | 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, V., Horwood, K., Comar, Manola, Bovenzi, Massimo, Dong L., F, Neuzili, J., Amati, M., Tomasetti, M., 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, Dong, Lan-Feng, Neuzil, Jiri, Amati, Monica, Tomasetti, Marco |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology Mesothelioma Cancer Research Pathology Lung Neoplasms Logistic regression Epigenetic biomarkers Epigenesis Genetic Carcinoembryonic antigen Epigenetic biomarker education.field_of_study biology Methylated Middle Aged miR-126 Early diagnosi Early diagnosis Prognosis Mesothelin Female Multidrug Resistance-Associated Proteins Lung cancer gene thrombomodulin miR-126a Pulmonary and Respiratory Medicine medicine.medical_specialty Population GPI-Linked Proteins Thrombomodulin Internal medicine Biomarkers Tumor medicine Humans education Aged Methylated gene thrombomodulin Receiver operating characteristic business.industry Mesothelioma Malignant Reproducibility of Results DNA Methylation medicine.disease MicroRNAs biology.protein business |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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