Format

Send to

Choose Destination
Lung Cancer. 2015 Dec;90(3):457-64. doi: 10.1016/j.lungcan.2015.09.021. Epub 2015 Sep 25.

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

Author information

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.

KEYWORDS:

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

PMID:
26431916
DOI:
10.1016/j.lungcan.2015.09.021
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center