Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis

Our plain-English summary of Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis, by E. Schillebeeckx, J.P. van Meerbeeck, K. Lamote (European Respiratory Review, 2021).

The study

• Authors: E. Schillebeeckx, J.P. van Meerbeeck, K. Lamote
• Journal: European Respiratory Review
• Published: 2021;30(162)
• Type of article: Meta-analysis, Systematic review
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.

Copyright ©The authors 2021.

In plain English

This article was a systematic review and meta-analysis of published studies that tested markers in body fluids, mainly blood and pleural fluid, for diagnosing malignant pleural mesothelioma (MPM). The authors searched PubMed and Web of Science for articles published before 31 December 2019. They included 100 articles and pooled results from 56. Accuracy was reported as the area under the curve (AUC), a measure of how well a test told MPM patients apart from comparison groups. Pooled over 27 studies, serum mesothelin gave an AUC of 0.81 (95% confidence interval 0.79 to 0.83). Plasma fibulin-3, from three studies, gave 0.91 (0.86 to 0.97), the highest for plasma. Fibulin-3 in pleural fluid gave 0.68 (0.50 to 0.87). Serum HMGB1 did not distinguish MPM patients from asbestosis patients. The authors noted that the included studies used varied control groups, often did not set cut-off values in advance, and mostly included already diagnosed patients with advanced disease. The authors concluded that plasma fibulin-3 was the most promising single marker and called for larger validation studies.

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: Systematic review and meta-analysis of diagnostic accuracy studies; all included studies had a cross-sectional, case-control design
• Who was studied: 100 published articles (56 pooled in the meta-analysis) comparing MPM patients with various control groups, published before 31 December 2019, from PubMed and Web of Science
• Exposure: Not an asbestos exposure study. It reviewed diagnostic markers measured in body fluids (serum, plasma, pleural effusion, urine). Control groups in the included studies ranged from healthy people with and without proven asbestos exposure to patients with asbestos-related benign disease, other cancers and other benign diseases.
• Main results:
  • Serum mesothelin: summary AUC of 0.81 (95% CI 0.79 to 0.83) when 27 studies were combined
  • Plasma fibulin-3: summary AUC of 0.91 (95% CI 0.86 to 0.97) from three studies, the highest for plasma
  • Plasma mesothelin: overall AUC of 0.86 (95% CI 0.79 to 0.92)
  • Pleural effusion mesothelin: 19 studies with AUC values from 0.70 to 0.93, summary 0.83 (95% CI 0.81 to 0.85)
  • Pleural effusion fibulin-3: summary AUC of 0.68 (95% CI 0.50 to 0.87); the authors judged it not a good standalone marker
  • Serum HMGB1: no differences were found between MPM patients and asbestosis patients
  • In one included study, serum mesothelin gave an AUC of 0.74 when only stage I MPM patients were compared with asbestos-exposed controls, lower than 0.81 for all stages
• The authors' conclusion: The authors concluded that, based on this review, plasma fibulin-3 was the most promising single biomarker and should be the focus of further research
• Limitations the authors state:
  • Most included studies used limited discovery cohorts; clinical use would require larger validation studies
  • Protocols and control groups varied widely across the included studies
  • Cut-off values were often calculated from the study's own data rather than set in advance, a potential source of bias
  • Most studies included already diagnosed patients with mostly advanced disease, limiting their relevance to early detection and screening
  • The HMGB1 results rest on only two studies with limited sample sizes

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: Biomarker, Pleural Mesothelioma, Systematic Review, Meta-Analysis, Prognosis, Mesothelin, Fibulin-3.

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