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

Lory Santarelli, Sara Staffolani, Elisabetta Strafella, Linda Nocchi, Nicola Manzella, Paola Grossi, Massimo Bracci, Elettra Pignotti, Renata Alleva, Battista Borghi, Cecilia Pompili, Armando Sabbatini, Corrado Rubini, Lina Zuccatosta, Elisabetta Bichisecchi, Matteo Valentino, Keith Horwood, Manola Comar, Massimo Bovenzi, Lan Feng DongJiri Neuzil, Monica Amati, Marco Tomasetti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)457-464
Number of pages8
JournalLung Cancer
Issue number3
Publication statusPublished - Dec 1 2015


  • Early diagnosis
  • Epigenetic biomarkers
  • Lung cancer
  • Mesothelin
  • Mesothelioma
  • Methylated gene thrombomodulin
  • miR-126

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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