Lory Santarelli1, Sara Staffolani1, Elisabetta Strafella1, Linda Nocchi1, Nicola Manzella1, Paola Grossi1, Massimo Bracci1, Elettra Pignotti2, Renata Alleva2, Battista Borghi2, Cecilia Pompili3, Armando Sabbatini3, Corrado Rubini4, Lina Zuccatosta5, Elisabetta Bichisecchi6, Matteo Valentino1, Keith Horwood7, Manola Comar8, Massimo Bovenzi8, Lan-Feng Dong9, Jiri Neuzil10, Monica Amati1, Marco Tomasetti11. 1. Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy. 2. Department of Anesthesiology Research Unit, IRCCS Orthopaedic Institute Rizzoli, Bologna, Italy. 3. Division of Thoracic Surgery, United Hospitals, Ancona 60126, Italy. 4. Department of Biomedical Sciences and Public Health, Section of Anatomical Pathology, Polytechnic University of Marche, Ancona, Italy. 5. Pulmonary Diseases Unit, Department of Immunoallergic and Respiratory Diseases, United Hospitals, Ancona, Italy. 6. Division of Radiology, United Hospitals, Ancona, Italy. 7. Greenslopes Private Hospital, Qld, Australia. 8. Department of Medical Sciences, University of Trieste, Trieste, Italy. 9. Mitochondria, Apoptosis and Cancer Research Group, School of Medical Science and Griffith Health Institute, Griffith University, Southport, Qld, Australia. 10. Mitochondria, Apoptosis and Cancer Research Group, School of Medical Science and Griffith Health Institute, Griffith University, Southport, Qld, Australia; Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague 4, Czech Republic. 11. Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy. Electronic address: m.tomasetti@univpm.it.
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 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.
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.
Authors: Georg Johnen; Katarzyna Gawrych; Irina Raiko; Swaantje Casjens; Beate Pesch; Daniel G Weber; Dirk Taeger; Martin Lehnert; Jens Kollmeier; Torsten Bauer; Arthur W Musk; Bruce W S Robinson; Thomas Brüning; Jenette Creaney Journal: BMC Cancer Date: 2017-05-30 Impact factor: 4.430
Authors: A Bonotti; R Foddis; S Landi; O Melaiu; C De Santi; L Giusti; E Donadio; F Ciregia; M R Mazzoni; A Lucacchini; M Bovenzi; M Comar; E Pantani; A Pistelli; A Cristaudo Journal: Dis Markers Date: 2017-02-28 Impact factor: 3.434
Authors: Daniel G Weber; Katarzyna Gawrych; Swaantje Casjens; Alexander Brik; Martin Lehnert; Dirk Taeger; Beate Pesch; Jens Kollmeier; Torsten T Bauer; Georg Johnen; Thomas Brüning Journal: Dis Markers Date: 2017-02-21 Impact factor: 3.434