Biomarkers in the prevention and follow-up of workers exposed to asbestos

Our plain-English summary of Biomarkers in the prevention and follow-up of workers exposed to asbestos, by R. Foddis, A. Bonotti, S. Landi, et al (Journal of Thoracic Disease, 2018).

The study

• Authors: R. Foddis, A. Bonotti, S. Landi, P. Fallahi, G. Guglielmi, A. Cristaudo
• Journal: Journal of Thoracic Disease
• Published: 2018;10(Suppl 2):S360-S368
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Although in most developed countries the use of asbestos is banned, there is still a consistent portion of the world where asbestos extraction, trading and manufacturing of asbestos-made products is largely diffuse. Worldwide, hundreds of millions of people are at risk of developing an asbestos caused disease because of occupational, environmental or domestic exposure. The WHO estimates that asbestos is responsible for more than 100,000 deaths yearly. This scenario has prompted the research on biomarkers potentially useful for early diagnosis, prognosis and preventive programs on exposed population as well. Here we reviewed the up-to-date literature on this field of research highlighting that along with mesothelin and osteopontin (OPN), some more recently investigated molecules, such as high mobility group box 1 (HMGB1) protein, fibulin-3 and some miRNAs showed very promising. Most of the carried-out studies showed an interesting diagnostic and prognostic performance of some biomarkers, but since they usually lack adequate either specificity or sensitivity, their use in screening or in preventive programs is still not recommended on a routine basis. However, this review suggests the need for more reliable experimental design involving larger population and preferring longitudinal screening of asbestos exposed individuals rather than a single baseline assessment investigation. In addition, given their better diagnostic accuracy, the use of panels including several biomarkers is highly recommended.

In plain English

This article was a review of earlier research, not a new study. The authors summarized published work on biomarkers (measurable molecules, mostly in blood) that might help detect, monitor or predict malignant pleural mesothelioma (MPM) in people exposed to asbestos. It covered mesothelin (SMRP), osteopontin, megakaryocyte potentiating factor, fibulin-3, HMGB1 protein, BAP1 gene mutations and microRNAs. In the studies cited, SMRP distinguished the epithelioid type of MPM from controls with a specificity of 80–85% and a less consistent sensitivity of 60–90%. A cited meta-analysis of fibulin-3 reported a pooled sensitivity of 62% at a specificity of 82% after outlier adjustment. In an earlier study by the authors' group of 43 asbestos-exposed subjects and 27 people with epithelioid MPM, a panel of six markers reached 85.7% specificity and 100% sensitivity. The authors stated that biomarkers for routine early diagnosis and screening were not yet available. The authors concluded that some blood biomarkers, especially combined in panels, are very promising for prevention and that further research is highly recommendable.

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 literature
• Who was studied: Published research on biomarkers for asbestos-related disease, mainly malignant pleural mesothelioma (MPM). The article does not describe how studies were selected or how many were reviewed.
• Exposure: Asbestos exposure in general (occupational, environmental or domestic). Specific fiber types were not distinguished.
• Main results:
  • In the studies cited, SMRP (soluble mesothelin-related peptides) distinguished epithelioid MPM from controls with a specificity of 80–85% and a less consistent sensitivity of 60–90%.
  • A cited review of serum osteopontin for distinguishing MPM from controls reported a pooled sensitivity of 57% and a pooled specificity of 81%.
  • A cited meta-analysis of fibulin-3 by Pei et al., covering six studies with 468 MPM patients and 664 controls, reported a pooled sensitivity of 62% at a specificity of 82% after outlier adjustment.
  • A cited study by Napolitano et al. reported 100% sensitivity for hyperacetylated HMGB1 in diagnosing mesothelioma, among 22 cases and 20 healthy volunteers. The authors said these results need confirmation in a larger population.
  • In a 2011 study by the authors' group, combining serum mesothelin with plasma osteopontin gave an AUC (a measure of diagnostic accuracy) of 0.873. This was higher than osteopontin alone (0.795) or SMRP alone (0.62).
  • In an earlier study by the authors' group of 43 asbestos-exposed subjects and 27 people with epithelioid MPM, a six-marker panel reached a specificity of 85.7% and a sensitivity of 100% at a cut-off of 0.13. The six markers were SMRP, plasma osteopontin, IL6, vimentin, desmin and HGF.
  • The authors stated that biomarkers for routine early diagnosis and screening were not yet available.
• The authors' conclusion: The authors concluded that some blood biomarkers, especially when combined in panels, are very promising in prevention as well, and that further research is highly recommendable.
• Limitations the authors state:
  • The authors noted that the microRNA studies they reviewed lacked sufficient overall consistency.
  • The authors noted that because MPM is rare, the share of test-positive people who actually have the disease (positive predictive value) will be low, even with accurate tests.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Mesothelin, Osteopontin, High Mobility Group Box 1 (HMGB1), Fibulin-3.

Related studies

• Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations — E. Pluygers, P. Baldewyns, et al. (1992)
• Biomarker assessments in asbestos-exposed workers as indicators for selective prevention of mesothelioma or bronchogenic carcinoma: rationale and practical implementations — E. Pluygers, P. Baldewyns, et al. (1991)
• Asbestos exposure biomarkers in the follow-up of asbestos-exposed workers — V. Paolucci, R. Romeo, et al. (2018)
• Serum mesothelin and other biomarkers: what have we learned in the last decade? — A. Cristaudo, A. Bonotti, et al. (2018)
• A Novel Panel of Serum Biomarkers for MPM Diagnosis — A. Bonotti, R. Foddis, et al. (2017)
• Putative Biomarkers for Malignant Pleural Mesothelioma Suggested by Proteomic Analysis of Cell Secretome — S. Lacerenza, F. Ciregia, et al. (2020)

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