Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers

Our plain-English summary of Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers, by C. Sorino, M. Mondoni, G. Marchetti, et al (Journal of Clinical Medicine, 2023).

The study

• Authors: C. Sorino, M. Mondoni, G. Marchetti, S. Agati, R. Inchingolo, F. Mei, S. Flamini, F. Lococo, D. Feller-Kopman
• Journal: Journal of Clinical Medicine
• Published: 2023;12(22)
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

In plain English

This article was a non-systematic narrative review of published research on blood and pleural fluid biomarkers for pleural mesothelioma, a cancer the authors described as associated with asbestos exposure. The authors searched PubMed and the Cochrane Library up to 26 August 2023, plus ClinicalTrials.gov, and collected no new data. They reported that a meta-analysis of 19 studies found an overall AUCROC (a measure of how well a test separates patients from non-patients) of 0.83 (95% CI 0.81 to 0.85) for mesothelin in pleural effusion. A patient-data meta-analysis of serum mesothelin in 4491 patients estimated 47% sensitivity and 95% specificity. They described fibulin-3 diagnostic findings as unconfirmed or conflicting and microRNA results as heterogeneous. They called calretinin findings promising, and called osteopontin a biomarker with validated prognostic power despite low diagnostic specificity. They noted concerns about data integrity in one HMGB1 study. MESOMARK, a serum SMRP test, was the only FDA-approved biomarker test for mesothelioma, they reported. The authors concluded that none of the biomarkers they reviewed were "ready for prime time". They added that there was still no evidence early detection improves treatment outcomes.

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: Non-systematic narrative literature review
• Who was studied: Published articles found in PubMed and the Cochrane Library from the start of those databases to 26 August 2023, plus ongoing trials listed on ClinicalTrials.gov (searched 30 October 2023). The review covered studies of pleural mesothelioma patients and comparison groups.
• Exposure: The review studied biomarkers in blood and pleural fluid, not asbestos exposure. It names no fiber types or doses. In background, the authors state that most pleural mesothelioma cases are associated with asbestos exposure.
• Main results:
  • Pleural fluid mesothelin: the review reported that a meta-analysis by Schillebeeckx et al. included 19 studies, with an overall AUCROC of 0.83 (95% CI: 0.81 to 0.85).
  • Serum mesothelin: the review reported that a patient-data meta-analysis of 4491 patients estimated sensitivity at 47%, specificity at 95%, and an AUCROC of 0.77.
  • Pleural fluid fibulin-3: the review reported an overall AUCROC of 0.68 (95% CI: 0.50 to 0.87) in the Schillebeeckx et al. meta-analysis. Early plasma fibulin-3 results reported by Pass et al. were not confirmed by later studies.
  • Osteopontin: the review reported low specificity for diagnosis when compared with benign pleural effusions and other diseases. In its conclusions, it called osteopontin a biomarker with validated prognostic power.
  • Calretinin: the review described promising findings for early diagnosis and for distinguishing PM patients from asbestos-exposed and healthy controls.
  • Calretinin with mesothelin: in a cited prospective cohort of subjects with benign asbestos-related diseases, the combination detected mesothelioma up to about a year before clinical diagnosis with 46% sensitivity and 98% specificity.
  • SMRP and survival: the review reported conflicting evidence. A meta-analysis of 8 studies of 579 patients linked high SMRP levels with worse survival, but later studies did not confirm this.
  • HMGB1: the review noted that an investigation raised concerns about data integrity in one study of this marker. It also reported no difference between patients with mesothelioma and patients with asbestosis (AUCROC 0.56).
  • As of October 2023, the review reported that MESOMARK was the only FDA-approved biomarker test for mesothelioma.
• The authors' conclusion: The authors concluded that none of the biomarkers they reviewed were ready for prime time and that further research is needed. They also stated there is still no evidence that early detection improves treatment outcomes for pleural mesothelioma patients.
• Limitations the authors state:
  • The authors noted that results of the microRNA and long non-coding RNA studies were heterogeneous. They attributed this to diverse control groups, small sample sizes and non-standardized detection methods.
  • The authors noted that early breath-analysis studies had small samples and no external validation, so their findings cannot yet be generalized.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Prognosis, Staging, Histological Subtype, Pleural Effusion, Mesothelin, Non-epithelioid.

Related studies

• Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma — H.I. Pass, S.M. Levin, et al. (2012)
• Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study — D.G. Weber, G. Johnen, et al. (2012)
• Calretinin as a blood-based biomarker for mesothelioma — G. Johnen, K. Gawrych, et al. (2017)
• Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects — S. Guarrera, C. Viberti, et al. (2019)
• Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy — W.L. Chin, A.M. Cook, et al. (2025)
• Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis — C. Jiménez-Ramírez, D. Gilbert Weber, et al. (2022)

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