Serum mesothelin and other biomarkers: what have we learned in the last decade?

Our plain-English summary of Serum mesothelin and other biomarkers: what have we learned in the last decade?, by A. Cristaudo, A. Bonotti, G. Guglielmi, et al (Journal of Thoracic Disease, 2018).

The study

• Authors: A. Cristaudo, A. Bonotti, G. Guglielmi, P. Fallahi, R. Foddis
• Journal: Journal of Thoracic Disease
• Published: 2018;10(Suppl 2):S353-S359
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In the last decade there is been much interest in noninvasive, economic and well-accepted diagnostic tests for screening of subjects exposed to asbestos, and in patients with malignant pleuric mesothelioma (MPM) for diagnosis or monitoring response to treatment. Several biomarkers have been suggested as tools for screening and early diagnosis of MPM. Currently, in patients with MPM, have been reported high levels of soluble mesothelin-related peptides (SMRP), plasmatic osteopontin (pOPN), vimentin, fibulin-3 and many others as promising marker for diagnosis, even their use in prevention monitoring is still discussed. In this type of disease, a key role could be played by miRNAs, which expression has been investigated in a large series of MPM to examine new pathways useful in diagnosis, prognosis and therapy. An altered expression of some proteins has been reported, useful as biomarkers, in comparative proteomic analysis of malignant pleural mesothelioma. New promising markers are nowadays under study and alone or better in combination, they'll be very helpful in diagnosing, monitoring mesothelioma patients or for screening of risk groups.

In plain English

This is a review article describing published research on blood and pleural-fluid markers (biomarkers) for malignant pleural mesothelioma (MPM), both in patients and in people exposed to asbestos. It did not report a new study, and it did not describe how the studies it discussed were chosen. For soluble mesothelin-related peptides (SMRP), the review reported three findings. High levels were found only in epithelioid and mixed MPM. A pooled analysis by Hollevoet and colleagues found that a negative SMRP blood test does not rule out MPM. Mesothelin's sensitivity of 35–50% limits its value for diagnosis. The review also discussed osteopontin, fibulin-3, microRNAs, chemokines and other markers. It noted that one study found fibulin-3 less sensitive than SMRP and that microRNAs still need standardized validation. The authors concluded that SMRP is the only FDA-approved biomarker. They added that combining markers could improve accuracy, that larger and better-designed studies are needed, and that the current status of MPM biomarkers is "not satisfactory but encouraging."

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 (no methods for selecting studies described)
• Who was studied: Published studies of biomarkers in patients with malignant pleural mesothelioma and in people exposed to asbestos, using serum, plasma and pleural effusions
• Exposure: Asbestos exposure in general (no fiber types specified); the review concerns biomarker tests for screening asbestos-exposed people and for diagnosing and monitoring MPM
• Main results:
  • Across the SMRP studies reviewed, high SMRP levels were found only in epithelioid and mixed MPM
  • A meta-analysis by Hollevoet et al. found that a negative SMRP blood test does not exclude MPM in symptomatic or high-risk individuals
  • The cited sensitivity of mesothelin was 35–50%, which limits its diagnostic value
  • The authors' own earlier data suggested that age, smoking and asbestos exposure do not influence plasma or serum osteopontin, and that plasma osteopontin is more stable than serum osteopontin
  • Creaney et al. found fibulin-3 increased in the plasma of MPM patients, but with lower sensitivity than previously reported and inferior to SMRP
  • Several microRNAs were proposed as markers, but the review stated that standardized validation studies are still needed
  • In a cited study, levels of the chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases
• The authors' conclusion: The authors concluded that SMRP is the only FDA-approved MPM biomarker for diagnostic and prognostic purposes. They noted that the Helsinki criteria made no specific recommendations for screening with these markers, and they called the current status of MPM biomarkers not satisfactory but encouraging.
• Limitations the authors state:
  • The authors stated that additional studies with more patients and better design are needed to assess the diagnostic power of these biomarkers
  • The authors noted that no specific recommendations have been made for using these biomarkers for screening

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Biomarker, Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Osteopontin, Fibulin-3, Prognosis, Pleural Mesothelioma.

Related studies

• Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos? — V.C. Sanchez, J.R. Pietruska, et al. (2009)
• Twenty-five years of fiber analysis: what have we learned? — V.L. Roggli, R.T. Vollmer (2008)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein — A. Cristaudo, R. Foddis, et al. (2010)
• Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer — A. Cristaudo, R. Foddis, et al. (2007)
• 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)

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