Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Our plain-English summary of Diagnostic and prognostic biomarkers for malignant mesothelioma: an update, by Z. Chen, G. Gaudino, H.I. Pass, et al (Translational Lung Cancer Research, 2017).

The study

• Authors: Z. Chen, G. Gaudino, H.I. Pass, M. Carbone, H. Yang
• Journal: Translational Lung Cancer Research
• Published: 2017;6(3):259-269
• Type of article: Review
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease. However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies. Here we review the most promising biomarkers in MM to date: mesothelin, soluble mesothelin-related peptides (SMRPs), megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1), microRNAs (miRNAs), multiplex protein signatures. The validation of these biomarkers will allow their use, alone or in combination, for monitoring individuals from cohorts at risk of MM and attaining early detection of MM that is instrumental in improving patient survival.

In plain English

This article was a review, not a new study. The authors summarized published research on tests (biomarkers) that might help diagnose malignant mesothelioma earlier. Serum soluble mesothelin-related peptides (SMRPs) are the only FDA-approved diagnostic marker, and they were approved only to monitor tumor recurrence after therapy. One cited meta-analysis of 12 studies reported 64% sensitivity (95% CI 61–68%) and 89% specificity (95% CI 88–90%) for them. Another, of 16 studies, reported 32% sensitivity (95% CI 26–40%) and 95% specificity. A cited osteopontin meta-analysis reported pooled sensitivity of 57% (95% CI 52–61%) and specificity of 81% (95% CI 79–84%). One of fibulin-3 reported 62% (95% CI 45–77%) and 82% (95% CI 73–89%). In the authors' own earlier study, serum hyperacetylated HMGB1 separated mesothelioma patients from asbestos-exposed and healthy people with 100% sensitivity and specificity, and validation was in progress. A cited protein-panel study of 117 patients and 142 asbestos-exposed controls reported an AUC of 0.99. The authors stated that current biomarkers have relatively poor sensitivity and specificity. They concluded that a combination of validated markers may allow earlier, more accurate diagnosis.

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 diagnostic and prognostic biomarkers for malignant mesothelioma
• Who was studied: No new patients were studied. The review covered published studies of mesothelin/SMRPs, MPF, osteopontin, fibulin-3, HMGB1, microRNAs and multiplex protein signatures.
• Exposure: Not an exposure study. As background, the authors state that malignant mesothelioma is mostly related to inhalation of asbestos and erionite fibers.
• Main results:
  • Serum SMRPs are described as the only FDA-approved diagnostic biomarker for malignant mesothelioma, with low sensitivity, and they were approved only to monitor tumor recurrence after therapy.
  • A cited meta-analysis of 12 studies (717 MM patients, 2,851 control subjects) reported 64% sensitivity (95% CI 61–68%) and 89% specificity (95% CI 88–90%) for serum SMRPs.
  • The cited Hollevoet et al. meta-analysis of 16 studies (4,491 controls, 1,026 MM patients) reported a sensitivity of 32% (95% CI 26–40%) and a specificity of 95% for mesothelin.
  • In a cited prospective multicenter study of 507 participants, SMRPs and MPF did not differ significantly in diagnostic performance (SMRPs 0.871, MPF 0.849; P=0.28).
  • A cited meta-analysis of serum osteopontin reported pooled sensitivity of 57% (95% CI 52–61%), specificity of 81% (95% CI 79–84%) and an AUC of 0.80.
  • A cited meta-analysis of fibulin-3 (7 studies, 468 MM cases) reported pooled sensitivity of 62% (95% CI 45–77%) and specificity of 82% (95% CI 73–89%).
  • In the authors' own earlier cited study, serum hyperacetylated HMGB1 distinguished MM patients from asbestos-exposed individuals and healthy controls with 100% sensitivity and specificity. Validation studies were stated to be in progress.
  • In a cited case-control study of 117 MM patients and 142 asbestos-exposed controls, a 13-marker protein classifier gave an AUC of 0.99 with sensitivity and specificity above 90%. Mesothelin in the same study gave an AUC of 0.82, sensitivity 66% and specificity 88%.
  • The authors stated that currently available tissue and blood biomarkers have relatively poor sensitivity and specificity.
• The authors' conclusion: The authors concluded that a combination of the best-performing markers, once validated by ongoing studies, may allow more accurate and earlier diagnosis of malignant mesothelioma.

Topics

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

Related studies

• Plasma Biomarker Enrichment of Clinical Prognostic Indices in Malignant Pleural Mesothelioma — H.I. Pass, C. Goparaju, et al. (2016)
• Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma — F. Mundt, H.J. Johansson, et al. (2014)
• Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study — S. Tsim, C. Kelly, et al. (2016)
• Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide — N. Dipalma, V. Luisi, et al. (2011)
• Assessment of Glutathione Peroxidase-1 (GPX1) Gene Expression as a Specific Diagnostic and Prognostic Biomarker in Malignant Pleural Mesothelioma — A.F. Gharib, M. Alaa Eldeen, et al. (2021)
• Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers — J. Creaney, I.M. Dick, et al. (2016)

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