Biomarkers for early detection of malignant mesothelioma: diagnostic and therapeutic application

Our plain-English summary of Biomarkers for early detection of malignant mesothelioma: diagnostic and therapeutic application, by M. Tomasetti, L. Santarelli (Cancers, 2010).

The study

• Authors: M. Tomasetti, L. Santarelli
• Journal: Cancers
• Published: 2010;2(2):523-48
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries.

In plain English

This article reviewed published research on biomarkers (substances measured in blood, fluid or tissue) for early detection, outlook and treatment response in malignant mesothelioma (MM). It reported no new study of its own, though it described some of the authors' unpublished data. In reviewed studies, 8OHdG, a DNA-damage marker in blood cells, separated asbestos-exposed workers from age-matched controls but not from MM patients. The authors judged standard tumour markers not sensitive or specific enough for clinical use. Osteopontin was raised in several other cancers, which the authors said limits its use. A meta-analysis of soluble mesothelin-related peptides (717 patients with MM, 2851 without) reported sensitivity of 64% and specificity of 89%. A large prospective study indicated these peptides are unlikely to be useful for screening. A study whose authors included both review authors reported that combining 8OHdG, VEGF and mesothelin peptides gave an accuracy score (area under the curve) of 0.925, plus or minus 0.035 (a spread the table does not define), for separating asbestos-exposed subjects from controls. The authors called for larger prospective studies to validate these markers.

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 biomarkers for malignant mesothelioma, including some of the authors' own unpublished data
• Who was studied: No single study population. The review covered studies of MM patients, asbestos-exposed subjects (people at high risk of the disease), patients with other cancers, and healthy controls.
• Exposure: Asbestos exposure, described as usually occupational. The review does not separate results by fiber type.
• Main results:
  • In reviewed studies, the DNA-damage marker 8OHdG in blood lymphocytes separated asbestos-exposed people from age-matched controls but not from MM patients.
  • In the authors' own unpublished data (42 asbestos-exposed subjects, 25 MM patients, 30 age-matched subjects), DNA repair rate did not differ between asbestos-exposed subjects and unexposed controls, but DNA repair was significantly delayed in MM patients.
  • The authors judged standard tumour markers (hyaluronic acid, cytokeratin fragments, cancer antigens) not sensitive or specific enough for clinical use.
  • In the first osteopontin study reviewed (69 asbestos-exposed subjects, 45 unexposed subjects, 76 MM patients), osteopontin had a sensitivity of 77.6% and a specificity of 85.5% at a cut-off of 48.3 ng/mL for separating exposed people with early MM from exposed people without it.
  • Osteopontin was over-expressed in several other cancers, and the authors said this lack of specificity limits its clinical use for MM.
  • A meta-analysis of soluble mesothelin-related peptides (717 patients with MM, 2851 without MM) reported a sensitivity of 64% (range 41 to 91%) and a specificity of 89% (range 73 to 100%).
  • A large prospective study of asbestos-exposed workers indicated that soluble mesothelin-related peptides are unlikely to be useful for screening.
  • The authors described soluble mesothelin-related peptides as suitable for diagnosing existing MM but not for predicting the disease.
  • In a study listed as reference 24, whose authors include both review authors (54 control subjects, 94 asbestos-exposed subjects, 22 MM patients), combining 8OHdG, VEGF and soluble mesothelin-related peptides increased discrimination between high-risk subjects and healthy controls.
  • In that study, the combined 8OHdG, VEGF and mesothelin-peptide panel had an area under the curve of 0.925, plus or minus 0.035, for controls versus asbestos-exposed subjects. The table does not say what the plus-or-minus figure represents. An area of 1.0 means perfect discrimination and 0.5 means no better than chance.
• The authors' conclusion: The authors concluded that larger prospective studies in independent samples, with rigorous statistics and standardized laboratory methods, are needed to validate diagnostic and prognostic biomarkers for MM.
• Limitations the authors state:
  • 8OHdG was measured in blood lymphocytes, not in the mesothelial cells where the tumour arises.
  • Studies using serum mesothelin to monitor treatment recruited small numbers of patients, so the authors said their findings should be interpreted with caution.
  • Soluble mesothelin-related peptides and MPF lack sensitivity for non-epithelial subtypes of mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Malignant Mesothelioma, Asbestos Exposure.

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