Circulating biomarkers in malignant pleural mesothelioma

Our plain-English summary of Circulating biomarkers in malignant pleural mesothelioma, by G. Viscardi, D. Di Natale, M. Fasano, et al (Exploration of Targeted Anti-tumor Therapy, 2020).

The study

• Authors: G. Viscardi, D. Di Natale, M. Fasano, M. Brambilla, R. Lobefaro, A. De Toma, G. Galli
• Journal: Exploration of Targeted Anti-tumor Therapy
• Published: 2020;1(6):434-451
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor strictly connected to asbestos exposure. Prognosis is dismal as diagnosis commonly occurs in advanced stage. Radiological screenings have not proven to be effective and also pathological diagnosis may be challenging. In the era of precision oncology, validation of robust non-invasive biomarkers for screening of asbestos-exposed individuals, assessment of prognosis and prediction of response to treatments remains an important unmet clinical need. This review provides an overview on current understanding and possible applications of liquid biopsy in MPM, mostly focused on the utility as diagnostic and prognostic test.

© The Author(s) 2020.

In plain English

This article is a review, not a new study. The authors summarized published research on 'liquid biopsy' for malignant pleural mesothelioma (MPM), meaning tests that look for signs of the tumor in blood or pleural fluid instead of tissue. They covered proteins such as mesothelin, osteopontin, fibulin-3 and HMGB1. They also covered microRNAs, tumor DNA, circulating tumor cells, epigenetic markers, exosomes and immune cells. Many of the reviewed studies compared people with MPM to asbestos-exposed people or to people with other pleural diseases. The authors noted that mesothelin is the only blood test approved by the US Food and Drug Administration, for detecting recurrence after surgery or assessing response to therapy. They cited a pooled analysis of 16 studies in which, at a cut-off of 2.00 nmol/L, its sensitivity ranged from 19% to 68%. They described osteopontin as lacking specificity for MPM. The authors concluded that no single biomarker has reached enough accuracy for clinical use, and that none is recommended for screening. They noted that most markers were studied retrospectively in small groups of patients.

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 circulating (blood and pleural fluid) biomarkers in malignant pleural mesothelioma
• Who was studied: No new population. The review draws on published studies of MPM patients, asbestos-exposed subjects, healthy subjects, and patients with lung cancer or non-malignant pleural disease.
• Exposure: Not an exposure study. Asbestos exposure (occupational and/or environmental) is described as the main cause of MPM, and asbestos-exposed subjects serve as comparison groups in many reviewed studies. No fiber types are named.
• Main results:
  • The authors reported that mesothelin (SMRP) is the most studied marker and the only FDA-approved blood test, approved for detecting MPM recurrence after surgery or assessing response to therapy.
  • The authors cited a meta-analysis of 16 studies of serum mesothelin. At a cut-off of 2.00 nmol/L, sensitivity ranged from 19% to 68% and specificity from 88% to 100%.
  • The authors cited a meta-analysis of six studies of osteopontin. It reported sensitivity of 0.65 (95% CI 0.60 to 0.70) and specificity of 0.81 (95% CI 0.78 to 0.85).
  • The authors described fibulin-3 results as conflicting. A study of 192 patients by Creaney et al. reported sensitivity of 22% and specificity of 95% for plasma fibulin-3.
  • The authors cited a study by Tabata et al. comparing 61 MPM patients with 45 healthy asbestos-exposed individuals. In that study, serum HMGB1 had sensitivity of 34.4%, and specificity and positive predictive value of 100% each, at a cut-off of 9.0 ng/mL.
  • The authors summarized osteopontin as a marker of how long a person was exposed to asbestos, with a possible prognostic role, but lacking specificity for MPM.
• The authors' conclusion: The authors concluded that no single biomarker has reached enough accuracy for use in clinical practice. They also stated that there is no evidence that early detection of MPM improves survival, and that none of these biomarkers is recommended for screening.
• Limitations the authors state:
  • The authors noted that most biomarkers were studied retrospectively in small cohorts, and that differences in how samples were handled and tested weaken the conclusions.
  • For mesothelin as a prognostic marker, the authors noted small sample sizes and differing cut-off values and treatments across studies.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Asbestos Exposure, Prognosis, Liquid Biopsy.

Related studies

• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy — M. Tomasetti, M. Amati, et al. (2017)
• Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation — L. Ferrari, M. Carugno, et al. (2020)
• A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma — B.T.V. Duong, L. Wu, et al. (2020)
• Circulating microRNA-197-3p as a potential biomarker for asbestos exposure — F. Frontini, I. Bononi, et al. (2021)

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