Biomarkers for malignant pleural mesothelioma: current status

Our plain-English summary of Biomarkers for malignant pleural mesothelioma: current status, by L. Greillier, P. Baas, J.J. Welch, et al (Molecular Diagnosis & Therapy, 2008).

The study

• Authors: L. Greillier, P. Baas, J.J. Welch, B. Hasan, A. Passioukov
• Journal: Molecular Diagnosis & Therapy
• Published: 2008;12(6):375-90
• Type of article: Review
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose main etiology is exposure to asbestos fibers. The incidence of MPM is anticipated to increase worldwide during the first half of this century. For various reasons, MPM is difficult to diagnose and is notoriously refractory to most treatments. However, recently two active chemotherapy regimens have been demonstrated to significantly increase survival in patients with MPM, and several therapeutic agents and strategies are currently under evaluation.Researchers have actively sought MPM biomarkers for more than 20 years. Biomarkers would be helpful in managing three clinical aspects of MPM: early diagnosis, prognosis, and treatment outcome prediction. The aims of the present review are to summarize the published and recently presented data on MPM biomarkers and to identify the prospects for future translational research projects.Among the 'classical' diagnostic biomarkers measured in biological fluids, such as cytokeratins and cell surface antigens, none discriminate patients with MPM from those with other malignancies and nonmalignant diseases. Osteopontin, soluble mesothelin, and megakaryocyte potentiating factor (MPF) appear to be the most promising of the recent biomarkers, but are still subject to some limitations. Osteopontin lacks specificity for mesothelioma, while both soluble mesothelin and MPF lack sensitivity for detecting non-epithelial subtypes. Panels consisting of a small set of biomarkers do not improve the diagnostic yield, and results from molecular profiling are too preliminary to be brought into daily clinical practice. While a large number of biomarkers have been assessed in biological fluids and tumor tissue for their prognostic value, none have had a widespread impact on clinical practice. In contrast, data concerning predictive biomarkers are very limited, even though they are most interesting from the perspective of clinicians.Additional prospective studies, in large and independent samples of patients, with rigorous statistical methodology and standardized laboratory techniques are now warranted to validate and define the precise value of diagnostic and prognostic MPM biomarkers. Future research efforts should focus on biomarkers predictive of the efficacy and toxicity of standard chemotherapy. Translational research should be systematically incorporated into the design of clinical trials assessing new targeted agents in MPM.

In plain English

This article was a review, not a new study. The authors searched PubMed for publications on biomarkers for malignant pleural mesothelioma (MPM) from January 1988 through July 2008, plus abstracts from several medical meetings. They grouped the markers as diagnostic, prognostic or predictive. The authors reported that no 'classical' blood or pleural-fluid marker separated MPM from other cancers or non-cancer diseases. Osteopontin, soluble mesothelin and megakaryocyte potentiating factor (MPF) appeared most promising. However, osteopontin lacked specificity for mesothelioma, and soluble mesothelin and MPF lacked sensitivity for non-epithelial subtypes. Small panels of markers did not improve diagnosis. Studies of soluble mesothelin for screening asbestos-exposed people gave mixed results. In one cited study of 558 asbestos-exposed subjects, none of the 15 with raised levels was diagnosed with mesothelioma. No prognostic marker had entered routine practice, and data on predictive markers were very limited. The authors concluded that larger prospective studies with rigorous methods are needed. They also concluded that future research should focus on markers that predict how well standard chemotherapy works and how toxic it is.

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: Literature review
• Who was studied: Published studies on malignant pleural mesothelioma biomarkers found in PubMed, dated January 1988 to July 2008. The authors also reviewed abstracts from the 2007 and 2008 American Society of Clinical Oncology and American Thoracic Society meetings, the 31st European Society of Medical Oncology Congress (2006) and the 12th World Conference on Lung Cancer (2007).
• Exposure: Not an exposure study. The review covered blood, pleural-fluid and tumor-tissue biomarkers for MPM, a tumor the authors describe as often a consequence of asbestos exposure.
• Main results:
  • No 'classical' fluid-based biomarker distinguished patients with MPM from those with other malignancies or nonmalignant diseases.
  • Osteopontin, soluble mesothelin and MPF appeared the most promising recent diagnostic biomarkers.
  • Osteopontin lacked specificity for mesothelioma. Soluble mesothelin and MPF lacked sensitivity for non-epithelial subtypes.
  • Small panels of biomarkers did not improve diagnostic yield, and molecular profiling results were too preliminary for daily clinical practice.
  • Evidence on soluble mesothelin as a screening tool was mixed. In a cited prospective study of 558 asbestos-exposed subjects, none of the 15 subjects with elevated soluble mesothelin was diagnosed with mesothelioma.
  • No prognostic biomarker had entered routine clinical practice.
  • No studies had focused on predictive biomarkers for the key chemotherapy drugs used in MPM.
• The authors' conclusion: The authors concluded that additional prospective studies in large, independent patient samples, with rigorous statistics and standardized laboratory techniques, are needed to validate diagnostic and prognostic MPM biomarkers. They concluded that future research should focus on biomarkers that predict the efficacy and toxicity of standard chemotherapy.
• Limitations the authors state:
  • The authors noted that the prognostic biomarker studies they reviewed had been faulted for poor design, lack of standardization and reproducibility, and statistical deficiencies, including small sample sizes.
  • Biomarkers from different studies were compared only qualitatively, using reported areas under ROC curves or sensitivity and specificity.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Prognosis, Etiology, Chemotherapy, Osteopontin, Mesothelin, Mesothelioma.

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• Asbestos exposure biomarkers in the follow-up of asbestos-exposed workers — V. Paolucci, R. Romeo, et al. (2018)
• Mesothelin (MSLN) promoter is hypomethylated in malignant mesothelioma, but its expression is not associated with methylation status of the promoter — K. Tan, K. Kajino, et al. (2010)
• Biomarkers in malignant pleural mesothelioma: current status and future directions — T. Ahmadzada, G. Reid, et al. (2018)
• Serum and pleural fluid biomarkers for mesothelioma — J. Creaney, B.W. Robinson (2009)

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