Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best?

Our plain-English summary of Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best?, by J. Creaney, D. Yeoman, A.W. Musk, et al (Lung Cancer, 2011).

The study

• Authors: J. Creaney, D. Yeoman, A.W. Musk, N. de Klerk, S.J. Skates, B.W. Robinson
• Journal: Lung Cancer
• Published: 2011;74(1):55-60
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Blood-based markers for malignant mesothelioma (MM), particularly soluble mesothelin and osteopontin, are currently of great clinical interest. As there is some concern about the sensitivity of osteopontin in serum versus plasma, we compared them in the same patient population to mesothelin.

Methods: Soluble mesothelin and osteopontin concentrations were determined by commercial assays in blood samples from 66 patients with pleural MM, 47 patients with non-malignant asbestos-related lung or pleural disease, 42 patients with other benign pleural and lung diseases and 21 patients with lung cancer.

Results: Soluble mesothelin and osteopontin in serum and plasma were significantly elevated in MM patients compared to patients with benign lung and pleural disease. At a level of specificity of 95% relative to patients with benign disease, the sensitivity of mesothelin in serum and plasma at presentation with symptoms was 67%, and for osteopontin in the plasma was 40% and in the serum was 20% for MM patients. Combining the serum mesothelin and plasma osteopontin markers using a logistic regression model did not significantly increase the area under the receiver operator curve.

Conclusion: Plasma osteopontin has a superior diagnostic accuracy to serum. As the choice of blood sample type has limit effect on soluble mesothelin sensitivity, plasma should be collected for biomarker evaluation in patients suspected of having mesothelioma.

Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

In plain English

This study from Perth, Western Australia, compared two blood markers for malignant mesothelioma, soluble mesothelin and osteopontin, measured in matching serum and plasma samples. Samples came from 66 patients with pleural mesothelioma, 89 patients with benign lung or pleural disease (including 47 with asbestosis and/or pleural plaques), and 21 patients with lung cancer. The test cut-off was set so that 95% of benign patients tested negative. At that cut-off, mesothelin detected 67% of mesothelioma patients in both serum and plasma. Osteopontin detected 40% in plasma and 20% in serum. Plasma osteopontin separated mesothelioma from benign disease significantly better than serum osteopontin. Mesothelin did significantly better than osteopontin whichever sample type was used. Combining serum mesothelin with plasma osteopontin detected 76% of mesothelioma patients, but its overall accuracy was not significantly different from serum mesothelin alone. In samples from 15 people, plasma osteopontin showed no statistically significant change after up to ten freeze-thaw cycles. The authors concluded that a single plasma sample should be sufficient to measure both markers as supporting tests in patients suspected of having 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 accuracy study comparing blood biomarker levels in matching serum and plasma samples from patients with mesothelioma and comparison patients
• Who was studied: Patients presenting with symptoms at respiratory clinics of Sir Charles Gairdner Hospital or the Hollywood Specialist Centre in Perth, Western Australia. The groups were 66 patients with pleural malignant mesothelioma (7 biphasic; 59 predominantly epithelioid or diagnosed on immunocytological grounds) and 89 with benign pleural or lung disease (47 asbestosis and/or pleural plaques, 12 idiopathic pulmonary fibrosis, 12 non-malignant exudative effusions, 18 sarcoidosis). There were also 21 lung cancer cases. Collection dates are not stated.
• Exposure: The study did not measure asbestos exposure. It measured soluble mesothelin and osteopontin in serum and plasma using commercial ELISA kits. One comparison group had benign asbestos-related disease (asbestosis and/or pleural plaques).
• Main results:
  • With the cut-off set at 95% specificity, soluble mesothelin detected 67% of mesothelioma patients in both serum and plasma. Osteopontin detected 40% in plasma and 20% in serum.
  • For distinguishing mesothelioma patients from benign disease patients, the area under the curve (AUC) was: serum mesothelin 0.885 (95% CI 0.831–0.939); plasma mesothelin 0.864 (95% CI 0.801–0.928); serum osteopontin 0.639 (95% CI 0.545–0.733); plasma osteopontin 0.763 (95% CI 0.681–0.845).
  • The AUC for osteopontin was significantly higher in plasma than in serum.
  • The AUC for mesothelin was significantly higher than for osteopontin, whether serum or plasma was used.
  • Serum osteopontin levels did not differ between patients with mesothelioma, lung cancer, or asbestos-related benign lung and pleural disease.
  • Plasma soluble mesothelin was significantly higher in mesothelioma patients than in patients with benign asbestos-related disease, other benign pulmonary disease, and lung cancer (each p less than 0.0001).
  • Serum and plasma mesothelin levels were strongly correlated (r = 0.9077). Serum and plasma osteopontin levels showed a significant but low correlation (r = 0.3300).
  • Combining serum mesothelin and plasma osteopontin gave an AUC of 0.912 and a sensitivity of 76% at 95% specificity.
  • The combined AUC was not significantly different from serum mesothelin alone (p = 0.083) but differed from plasma mesothelin (p = 0.023).
  • Nine mesothelioma patients (14%) had elevated osteopontin but were negative for mesothelin.
  • In plasma samples from 15 individuals, there was no statistically significant difference in mean osteopontin concentration after one, two, five and ten freeze-thaw cycles compared with the original sample.
• The authors' conclusion: The authors concluded that plasma is superior to serum for measuring osteopontin, and that a single plasma specimen should be sufficient to evaluate both mesothelin and osteopontin as ancillary tests in patients suspected of having mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Osteopontin, Mesothelin, Mesothelioma, Lung Cancer, Biomarker.

Related studies

• Comparison between plasma and serum osteopontin levels: usefulness in diagnosis of epithelial malignant pleural mesothelioma — A. Cristaudo, R. Foddis, et al. (2010)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Changes of mesothelin and osteopontin levels over time in formerly asbestos-exposed power industry workers — M.K. Felten, K. Khatab, et al. (2014)
• Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma — I. Pantazopoulos, P. Boura, et al. (2013)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)

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