Diagnosis and prognosis-review of biomarkers for mesothelioma

Our plain-English summary of Diagnosis and prognosis-review of biomarkers for mesothelioma, by H.H. Sun, A. Vaynblat, H.I. Pass (Annals of Translational Medicine, 2017).

The study

• Authors: H.H. Sun, A. Vaynblat, H.I. Pass
• Journal: Annals of Translational Medicine
• Published: 2017;5(11):244
• Type of article: Review
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between 1940 and 1980. With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers.

In plain English

This article was a review, not a new study. The authors summarized published research on markers in blood, pleural fluid and tumor tissue (biomarkers) that might help diagnose malignant pleural mesothelioma (MPM) or predict how long patients survive. Markers covered included soluble mesothelin-related proteins (mesothelin), osteopontin, fibulin-3, HMGB1, micro-RNAs, a SOMAmer protein panel and blood-cell ratios. Results from the reviewed studies were mixed. A study by Hollevoet and colleagues found mesothelin had specificity of 96% but sensitivity of only 47%. An early osteopontin study was confirmed by some later studies but not by others. One fibulin-3 study reported sensitivity of 96.7% and specificity of 95.5%. A later analysis of two cohorts found plasma fibulin-3 raised in one cohort but not the other. Studies of the neutrophil-to-lymphocyte ratio gave conflicting results. The authors concluded that osteopontin, mesothelin, fibulin-3, HMGB1 and micro-RNAs showed the most potential. They said that unstandardized treatments and tests, and small patient numbers in some studies, limited the evidence. They called for combined, larger cohorts.

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 pleural mesothelioma; the article does not describe how studies were selected
• Who was studied: No single study population. The review covered recent published studies of biomarkers in MPM patients, often compared with asbestos-exposed people without mesothelioma, other patients, or healthy controls. A supplementary table lists the studies.
• Exposure: Asbestos in general, with no fiber types named. Many reviewed studies used asbestos-exposed people without MPM as a comparison group. As background, the authors stated that about 27.5 million people in the United States were occupationally exposed to asbestos between 1940 and 1979.
• Main results:
  • The review reported that a study by Hollevoet and colleagues found serum mesothelin, as a diagnostic marker for MPM, had specificity of 96% and sensitivity of 47%.
  • The review reported on a study by Pass and colleagues comparing 69 patients with asbestos-related non-malignant pulmonary disease and 76 patients with pleural mesothelioma. At a serum osteopontin cutoff of 48.3 ng/mL, sensitivity was 77.6% and specificity was 85.5%. Later studies confirmed this in some cases but not others.
  • The review reported on the osteopontin results being checked by other researchers: some later studies confirmed them and others did not.
  • The review reported that one study found plasma fibulin-3, at a cutoff of 52.8 ng/mL, had sensitivity of 96.7% and specificity of 95.5% for separating patients with and without MPM.
  • The review reported that a later retrospective analysis of two MPM cohorts found plasma fibulin-3 significantly raised in the Sydney cohort but not in the Vienna cohort.
  • The review reported that a study by Napolitano and colleagues found serum hyperacetylated HMGB1, at a cutoff of 2.0 ng/mL, had sensitivity and specificity of 100% in separating MPM patients from asbestos-exposed individuals and healthy controls.
  • The review reported on a study by Pass and colleagues of 129 resected MPM samples. In patients with epithelial histology, higher miRNA-29 expression went with overall survival of 21.6 months, compared with 9.1 months for low expression.
  • The review reported that Ostroff and colleagues found a candidate 13-protein SOMAmer panel for detecting MPM in asbestos-exposed individuals, with an AUC of 0.95 and overall accuracy of 92%.
  • The review reported on a retrospective study of 150 MPM patients. Those with a lymphocyte-to-monocyte ratio greater than 2.74 had median overall survival of 14 months, compared with 5 months for those below 2.74.
  • The review reported that studies of the neutrophil-to-lymphocyte ratio as a prognostic marker gave conflicting results.
• The authors' conclusion: The authors concluded that the markers showing the most potential were the most widely studied ones: osteopontin, mesothelin-related proteins, fibulin-3, HMGB1 and micro-RNAs. They said other markers need much more work and validation, and that much work remains.
• Limitations the authors state:
  • The authors stated that many of the reviewed studies lacked standardized treatments and assays, which may affect their results.
  • The authors stated that low patient numbers in some reviewed studies limit how conclusive the results are.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Biomarker, Mesothelioma, Pleural Mesothelioma, Asbestos Exposure, Latency, Median Overall Survival, Discovery.

Related studies

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• 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)
• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• Malignant Mesothelioma, BAP1 Immunohistochemistry, and VEGFA: Does BAP1 Have Potential for Early Diagnosis and Assessment of Prognosis? — E. Pulford, K. Huilgol, et al. (2017)
• Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma — W. Zhang, X. Wu, et al. (2015)

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