Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma

Our plain-English summary of Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma, by J. Creaney, D. Yeoman, Y. Demelker, et al (Journal of Thoracic Oncology, 2008).

The study

• Authors: J. Creaney, D. Yeoman, Y. Demelker, A. Segal, A.W. Musk, S.J. Skates, B.W. Robinson
• Journal: Journal of Thoracic Oncology
• Published: 2008;3(8):851-7
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: There is increasing interest in identifying a blood-based marker for the asbestos-related tumor, malignant mesothelioma. Three potential markers for mesothelioma are mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. The purpose of the current study was to directly compare these biomarkers in the same sample population, determining their sensitivity and specificity in establishing a diagnosis, and to determine if diagnostic accuracy for mesothelioma is improved by combining the data from all three markers.

Methods: Serum levels of mesothelin, MPF and osteopontin were determined by commercially available assays in 66 samples from patients with pleural malignant mesothelioma, 20 healthy individuals, 21 patients with asbestos-related lung or pleural disease, 30 patients presenting with benign pleural effusions and 30 patients with other malignancies.

Results: Serum levels of the three markers were elevated in mesothelioma patients. At a level of specificity of 95% relative to healthy controls and patients with benign asbestos related disease, the sensitivity for mesothelioma was 34% for MPF, 47% for osteopontin and 73% for mesothelin. Osteopontin and MPF were unable to differentiate patients with mesothelioma from patients with other malignancies or those presenting with transudative pleural effusions. Combining the data from the three biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone.

Conclusion: Serum mesothelin remains the most specific marker for the diagnosis of mesothelioma.

In plain English

This study, from Perth, Western Australia, compared three blood (serum) proteins proposed as markers for malignant mesothelioma: mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin. The authors measured all three in the same samples, using commercial test kits. Samples came from 66 patients with pleural malignant mesothelioma and from comparison groups: 20 healthy people (10 with asbestos exposure), 21 patients with asbestosis and/or pleural plaques, 30 patients with non-cancerous pleural effusions, and 30 patients with other cancers. Each marker's cut-off was set so that 95% of the healthy and benign asbestos-related disease groups tested negative. At that cut-off, the marker was positive in 34% of mesothelioma patients for MPF, 47% for osteopontin and 73% for mesothelin. MPF and osteopontin levels did not differ between mesothelioma patients and patients with lung cancer or with transudate or malignant effusions. Mesothelin levels were significantly higher in epithelial-type than in predominantly sarcomatoid mesothelioma. Combining the three markers in a statistical model was not significantly better than mesothelin alone. The authors concluded that serum mesothelin remains the most specific marker for diagnosing mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic biomarker comparison study: three serum markers measured in the same samples from mesothelioma patients and several control groups, with sensitivity and specificity compared and markers combined by logistic regression
• Who was studied: Serum samples from patients at respiratory clinics of Sir Charles Gairdner Hospital or the Hollywood Specialist Centre, Perth, Western Australia (Australian Mesothelioma Tissue Bank). The groups were: 66 patients with pleural malignant mesothelioma (9 predominantly sarcomatoid; 57 predominantly epithelioid or diagnosed on immunocytological grounds); 20 apparently healthy individuals (10 with and 10 without reported asbestos exposure); 21 patients with benign asbestos-related pulmonary disease; 30 patients with nonmalignant effusions; 20 people with effusions due to other malignancies; and 10 lung cancer patients without an effusion. Collection dates are not given.
• Exposure: Not an exposure study. The study measured three serum markers (mesothelin, MPF, osteopontin). Asbestos exposure appears only as a feature of control groups: 10 healthy asbestos-exposed people and 21 patients with asbestosis and/or pleural plaques. No fiber types, products, jobs or doses are given.
• Main results:
  • At 95% specificity relative to healthy controls and patients with benign asbestos-related disease, sensitivity for mesothelioma was 34% for MPF, 47% for osteopontin and 73% for mesothelin.
  • In distinguishing mesothelioma patients from healthy controls and patients with benign asbestos-related disease, the area under the ROC curve (AUC) was 0.614 (95% CI 0.508 to 0.721) for MPF, 0.757 (95% CI 0.666 to 0.848) for osteopontin and 0.915 (95% CI 0.869 to 0.968) for mesothelin. The AUC for mesothelin was significantly higher than for MPF or osteopontin.
  • MPF levels in mesothelioma patients did not differ from those in patients with lung cancer or with transudate or malignant effusions. The same was reported for osteopontin.
  • Serum mesothelin levels were significantly higher in mesothelioma patients than in healthy controls, people with benign asbestos-related disease, and patients with benign effusions, malignant effusions or lung cancer.
  • Within the mesothelioma group, serum mesothelin was significantly higher in tumors of epithelial-like histology than in those of predominantly sarcomatoid histology.
  • Combining the markers by logistic regression did not significantly improve on mesothelin alone. Combinations including mesothelin had AUCs of 90.7 to 91.5%, while the MPF plus osteopontin combination had an AUC of 74.5%.
• The authors' conclusion: The authors concluded that serum mesothelin remains the most specific marker for the diagnosis of mesothelioma. They also stated that adding MPF and osteopontin did not improve diagnostic accuracy over mesothelin alone.
• Limitations the authors state:
  • Osteopontin was measured in serum, where it may be cleaved by thrombin, so results may not reflect true blood levels. The authors said the choice of plasma, serum or other collection methods needs further study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Osteopontin, Mesothelin, Malignant Mesothelioma, Mesothelioma, Biomarker, Pleural Effusion.

Related studies

• Megakaryocyte potentiating factor as a tumor marker of malignant pleural mesothelioma: evaluation in comparison with mesothelin — K. Iwahori, T. Osaki, et al. (2008)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)
• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)

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