Comparison of mesothelin and fibulin-3 in pleural fluid and serum as markers in malignant mesothelioma

Our plain-English summary of Comparison of mesothelin and fibulin-3 in pleural fluid and serum as markers in malignant mesothelioma, by J. Creaney, I.M. Dick, B.W. Robinson (Current Opinion in Pulmonary Medicine, 2015).

The study

• Authors: J. Creaney, I.M. Dick, B.W. Robinson
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2015;21(4):352-6
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Malignant mesothelioma is an asbestos-induced, aggressive tumour, which frequently presents with pleural effusion. There are over 60 reported causes that can result in the development of a pleural effusion. Currently, there are no tumour biomarkers in widespread clinical use for the differential diagnosis of mesothelioma from other diseases. With the incidence of mesothelioma expected to continue to increase, it is timely to review the current status of effusion-based biomarkers for mesothelioma diagnosis.

Recent Findings: The majority of recent studies have evaluated soluble mesothelin in effusions in a diagnostic setting for mesothelioma. However, at high specificity, the sensitivity of the assay is limited to approximately 60% at the time of diagnosis. There is considerable research effort directed toward the identification of new markers for mesothelioma through a variety of genomic, proteomic and immunomic based platforms. One of the few new biomarkers to be identified through a biomarker discovery pipeline and evaluated in pleural effusions is fibulin-3. Preliminary results on the diagnostic accuracy of fibulin-3 have been inconsistent.

Summary: To date, soluble mesothelin remains the best available biomarker for mesothelioma and a positive result is clinically useful in patients with pleural effusions in whom the diagnosis is uncertain.

In plain English

This article was a review, not a new study. The authors surveyed published research on tests of pleural fluid (fluid around the lungs) and blood. These tests aim to tell malignant mesothelioma, which the authors called asbestos-induced, apart from other causes of fluid build-up. They reported that soluble mesothelin, at high specificity, detected about 60% of cases at diagnosis. For a newer marker, fibulin-3, the original 2012 study by Pass and colleagues reported a pleural fluid sensitivity of 84% and specificity of 93%; later studies conflicted. An Italian sub-study tested serum; assuming serum and plasma results were comparable, the authors estimated fibulin-3 was above the original 52 ng/ml plasma threshold in one of 14 mesothelioma patients. In the authors' own 2014 study, plasma fibulin-3 had a sensitivity of 22% (18/82) and a specificity of 95% (114/120), and 63% (22/35) of benign effusions exceeded the fluid threshold. The authors called for suitable control groups and pre-set thresholds. They concluded that soluble mesothelin remained the best available marker: a positive result is informative, but a negative one is not.

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: Narrative review of published studies on fluid- and blood-based biomarkers for diagnosing mesothelioma
• Who was studied: No patients of the article's own; it reviewed published studies (including the authors' earlier work) measuring biomarkers in pleural effusions and blood of mesothelioma patients and comparison groups
• Exposure: Not an exposure study. Asbestos is named as the cause of mesothelioma; the topic is diagnostic tests (soluble mesothelin, megakaryocyte potentiating factor, hyaluronic acid, fibulin-3)
• Main results:
  • Across recent studies reviewed, soluble mesothelin in effusions at high specificity had sensitivity limited to approximately 60% at diagnosis
  • In the original fibulin-3 study (Pass et al.), pleural effusion fibulin-3 had sensitivity 84% and specificity 93% at 346 ng/ml (plasma: over 96% sensitivity at 95% specificity at 52 ng/ml); the reviewers estimated sensitivity in that study's validation set was less than 40% at 95% specificity
  • In an Italian sub-study (Corradi et al.) of serum, the reviewers estimated, assuming serum and plasma results are consistent, that fibulin-3 was above the original 52 ng/ml plasma threshold in one of 14 mesothelioma patients (7%); all 23 lung cancer, 14 asbestosis and 23 control patients were below it
  • In the authors' own 2014 study, plasma fibulin-3 at 52 ng/ml had sensitivity 22% (18/82) and specificity 95% (114/120) in mesothelioma patients versus other cancers and benign conditions
  • In the same 2014 study, 63% (22/35) of benign effusions had fibulin-3 above the 346 ng/ml threshold
  • In a small Egyptian study (25 mesothelioma cases, 9 benign effusion cases), using internally determined thresholds, serum fibulin-3 had 100% sensitivity at 78% specificity versus nonmalignant effusions
• The authors' conclusion: The authors concluded that soluble mesothelin remains the best available biomarker; because its specificity is high but its sensitivity limited, a positive result is informative but a negative one is not, and a better biomarker has yet to be identified
• Limitations the authors state:
  • The authors noted that biomarker studies of mesothelioma need appropriate, documented control groups
  • The authors noted that validation studies should use predefined diagnostic thresholds rather than study-specific cut-offs

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Fibulin-3, Mesothelioma, Pleural Effusion, Biomarker, Differential Diagnosis, Discovery.

Related studies

• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• 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)
• 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)
• Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial — S.I. Katz, L. Roshkovan, et al. (2021)
• Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases — S. Tsim, L. Alexander, et al. (2021)
• Diagnostic value of mesothelin in pleural fluids: comparison with CYFRA 21-1 and CEA — R. Filiberti, S. Parodi, et al. (2013)

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