Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment

Our plain-English summary of Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment, by J. Creaney, B.W.S. Robinson (Chest, 2017).

The study

• Authors: J. Creaney, B.W.S. Robinson
• Journal: Chest
• Published: 2017;152(1):143-149
• Type of article: Review
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

In plain English

This article was a review, not a new study. The authors described published research on blood and fluid tests (biomarkers) for malignant mesothelioma, focusing on soluble mesothelin. They reported that in 2007 the US Food and Drug Administration approved the MESOMARK mesothelin test as a Humanitarian Use Device for monitoring epithelioid and biphasic mesothelioma. Summarising studies of patients with pleural effusions (fluid around the lung), they reported that elevated fluid mesothelin had a positive predictive value of over 57% when cell examination was inconclusive or negative. They noted that kidney impairment can raise serum mesothelin without cancer, and that some patients with advanced disease have no detectable serum mesothelin. Prospective studies of asbestos-exposed groups found false positive rates above 90%, so the authors reported that mesothelin did not help early detection. ENOX2 was a preliminary finding needing extensive validation, and independent studies had not confirmed the high accuracy first reported for fibulin-3. The authors concluded that mesothelin remains promising for diagnosis and monitoring but its low sensitivity limits screening. They added that new biomarkers are unlikely to be adopted soon without 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: Narrative review of published research on mesothelioma biomarkers, focusing on soluble mesothelin
• Who was studied: No study population of its own. The authors reviewed published studies, mostly case-control studies, of biomarkers in patients with malignant mesothelioma (mainly pleural), in patients with pleural effusions, and in asbestos-exposed individuals.
• Exposure: Not an exposure study. The article is about biomarkers, not asbestos exposure. It mentions asbestos exposure only in general terms and names no fiber types.
• Main results:
  • The authors describe their own earlier collaborative study (reference 8), not new work in this article. In that study, 37 out of 44 mesothelioma patients (printed as 87%) had significantly elevated serum levels of soluble mesothelin-related protein compared with control groups.
  • In 2007 the US FDA approved the MESOMARK serum mesothelin assay as a Humanitarian Use Device for monitoring epithelioid and biphasic mesothelioma.
  • Kidney (renal) impairment has been shown to raise serum mesothelin when no cancer is present.
  • Mesothelin is more sensitive when measured in pleural effusion fluid than in serum. In the studies of consecutive effusion patients summarised in Table 1, elevated effusion mesothelin had a positive predictive value of over 57% where cytology was reported as suspicious, atypical, non-malignant or non-diagnostic.
  • For monitoring, the authors cite their own earlier study (reference 20), in which a treatment-related fall in mesothelin predicted survival. Table 2 reports a median survival of 19 months for patients whose mesothelin fell after chemotherapy, compared with 5 months for those whose mesothelin rose (p less than 0.001).
  • Mesothelin is not useful for monitoring every patient, because some patients with advanced-stage mesothelioma have no detectable serum mesothelin.
  • Several prospective studies of asbestos-exposed groups found false positive rates above 90% when serum mesothelin was monitored. The authors stated that it therefore did not assist early detection of mesothelioma.
  • In a retrospective analysis, mesothelioma-specific ENOX2 isoforms were detected in the serum of asbestos-exposed individuals four to ten years before clinical diagnosis. The authors called this a preliminary finding that requires extensive validation.
  • The high diagnostic accuracy first reported for fibulin-3 was not confirmed by later independent studies.
• The authors' conclusion: The authors concluded that mesothelin remains one of the most promising biomarkers for diagnosing and monitoring malignant mesothelioma, but that its low sensitivity limits its use as a screening tool. They also concluded that newer biomarkers are unlikely to enter clinical use in the near future without validation studies.
• Limitations the authors state:
  • The authors note that the effusion studies summarised in Table 1 used different mesothelin cut-off values, so their sensitivity and specificity figures are not directly comparable.
  • The authors note that few studies have examined biomarkers in malignant peritoneal mesothelioma, and most included only small numbers of peritoneal cases.

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: Malignant Mesothelioma, Biomarker, Discovery, Pleural Mesothelioma, Asbestos Exposure, Mesothelioma, Prognosis, Median Survival.

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• Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — R.A. Stahel, W. Weder, et al. (2010)
• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• Individual predictors of increased serum mesothelin in asbestos-exposed workers — R. Filiberti, P. Marroni, et al. (2013)
• Emergency diagnosis of cancer and previous general practice consultations: insights from linked patient survey data — G.A. Abel, S.C. Mendonca, et al. (2017)

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