Discovery of new biomarkers for malignant mesothelioma

Our plain-English summary of Discovery of new biomarkers for malignant mesothelioma, by J. Creaney, I.M. Dick, B.W. Robinson (Current Pulmonology Reports, 2015).

The study

• Authors: J. Creaney, I.M. Dick, B.W. Robinson
• Journal: Current Pulmonology Reports
• Published: 2015;4(1):15-21
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an asbestos-induced, aggressive tumour with limited treatment options and very poor outcome. Currently, there are no tumour biomarkers in widespread clinical use for this disease. Soluble mesothelin is the most intensively investigated mesothelioma biomarker and has been approved by the US FDA primarily as a tool for monitoring patient response and progression. Mesothelin is elevated in the blood and effusions of patients with mesothelioma, and is rarely elevated in people with benign disease with normal renal function. However, the sensitivity of mesothelin limits its use as a stand-alone tool for the screening of the asymptomatic asbestos-exposed population-one of the primary aims of mesothelioma biomarker studies. Thus, there is an intense research effort focused on the identification of new and/or novel biomarkers for mesothelioma. Some of the challenges associated with biomarker discovery in mesothelioma are discussed.

In plain English

This narrative review by researchers in Western Australia reported no new studies with human or animal subjects. The authors discussed the search for biomarkers (blood and fluid tests) for malignant mesothelioma, which they called asbestos-induced. They noted that over twenty soluble biomarkers had been reported, but few had been independently validated or brought into clinical use. Fibulin-3, for example, looked highly accurate in other researchers' first study, but its sensitivity was lower in later sample sets: 40% in Canadian and 22% in Australian samples, at 95% specificity. In the authors' own earlier studies, two different test kits for the marker MPF gave sensitivities of 29% and 52% on matching samples, both at 95% specificity. Based on published assumptions about mesothelin levels in patients and controls, the authors estimated that a discovery experiment limited to ten case and control samples, with 100 samples for verification, would have had about a 50% chance of identifying mesothelin itself. The authors concluded that mesothelin remained the single best blood-based biomarker for mesothelioma, and they hoped a panel of markers might succeed.

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 with commentary; no new studies with human or animal subjects
• Who was studied: Published literature on soluble biomarkers for malignant mesothelioma. The authors also drew on publicly available mRNA and proteomic datasets and their own earlier and unpublished laboratory data. There was no study population of its own.
• Exposure: Not studied directly. Mesothelioma is described as asbestos-induced, and the asymptomatic asbestos-exposed population is named as a main intended target for biomarker screening. No fiber types are named.
• Main results:
  • Of the more than twenty soluble mesothelioma biomarkers reported in the literature, few had been independently validated or translated to the clinic.
  • In later sample sets from other studies, fibulin-3 sensitivity was estimated at 40% in Canadian samples and 22% in Australian samples, at 95% specificity.
  • In the authors' own earlier studies, two different ELISA kits for megakaryocyte potentiating factor (MPF) gave sensitivities of 29% and 52% in matching samples, at 95% specificity.
  • Using the assumptions of Skates and colleagues, the authors estimated that a discovery experiment limited to ten case and control samples, with 100 samples for verification, would have had approximately a 50% probability of identifying mesothelin.
  • In the authors' own unpublished data, mesothelin mRNA levels did not differ between mesothelioma cell lines and normal mesothelial cell cultures.
  • In the authors' own unpublished proteomic dataset, mesothelin was shown to be differentially expressed in only one of three experiments.
• The authors' conclusion: The authors concluded that, despite many reported biomarkers, mesothelin remained the single best blood-based biomarker for mesothelioma and the only one with FDA approval. They hoped that an approach using a panel of biomarkers might be successful.

Topics

Medical terms in this study, explained in our Lexicon: Discovery, Biomarker, Malignant Mesothelioma, Mesothelin, Mesothelioma.

Related studies

• Malignant Mesothelioma Biomarkers: From Discovery to Use in Clinical Practice for Diagnosis, Monitoring, Screening, and Treatment — J. Creaney, B.W.S. Robinson (2017)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers — J. Creaney, I.M. Dick, et al. (2016)
• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)
• Serum and pleural fluid biomarkers for mesothelioma — J. Creaney, B.W. Robinson (2009)
• Association of biomarker levels with severity of asbestos-related diseases — E.K. Park, D.H. Yates, et al. (2012)

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