Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study

Our plain-English summary of Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study, by S. Casjens, D.G. Weber, G. Johnen, et al (BMJ Open, 2017).

The study

• Authors: S. Casjens, D.G. Weber, G. Johnen, I. Raiko, D. Taeger, C. Meinig, S. Moebus, K.H. Jöckel, T. Brüning, B. Pesch
• Journal: BMJ Open
• Published: 2017;7(10):e017104
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Mesothelin and calretinin are blood-based markers for malignant mesothelioma. The objective of this study was to analyse the markers in plasma samples from cancer-free men and to identify factors influencing their concentrations to minimise false-positive test results when using these markers for the early detection of malignant mesothelioma.

Setting: The present analyses used data and archived blood samples of the population-based Heinz Nixdorf Recall Study among elderly people collected from 2011 to 2014.

Participants: A total of 569 men (median age 70 years) without a malignant disease at the time of blood sampling were selected for these analyses.

Primary And Secondary Outcome: Mesothelin and calretinin concentration in plasma samples.

Results: We observed 24 mesothelin concentrations ≥1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%) and 34 calretinin concentrations ≥1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to 95.7%). Only five men had both markers above these cut-offs. Renal dysfunction and hypertension were major predictors of elevated mesothelin in addition to age. Regarding calretinin, the effect of renal dysfunction was slightly weaker and hypertension was not associated with increased concentrations. However, a diagnosis of cancer after blood collection and bronchial asthma were associated with positive calretinin results.

Conclusions: The combined determination of mesothelin and calretinin results in only few false-positive marker tests. Both markers are mainly influenced by renal dysfunction. The determination of cystatin C concentrations may be informative when interpreting the test results.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In plain English

This study measured two blood markers proposed for detecting malignant mesothelioma, mesothelin and calretinin, in stored plasma from 569 men in the Heinz Nixdorf Recall Study, a population-based cohort in Germany's Ruhr area, sampled in 2011 to 2014. None had a malignant disease when blood was drawn. The men came from the general population, not from a cohort of asbestos workers. The authors looked for factors linked to positive results in these cancer-free men. Mesothelin was at or above 1.5 nM in 24 men (4.2%) and calretinin at or above 1.0 ng/mL in 34 men (6.0%). Only five men were positive on both, which the authors reported as a specificity of 99.1% (95% CI 97.9% to 99.7%) for the two markers combined. In combined analyses, raised cystatin C (a kidney-function measure), hypertension and age were associated with positive mesothelin. Raised cystatin C, a cancer diagnosed after blood collection, and bronchial asthma were associated with positive calretinin; hypertension was not. The authors concluded that calretinin might be a useful adjunct to mesothelin for early detection. They noted the analyses rested on small numbers and included only men.

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: Analysis of archived blood samples and data from a prospective population-based cohort study, looking at predictors of positive marker tests (prevalence odds ratios from univariate and multiple logistic regression)
• Who was studied: 569 men from the second follow-up survey (2011 to 2014) of the Heinz Nixdorf Recall Study, a population-based cohort in the Ruhr area of Germany. Median age was 70 years (range 56 to 84). None had a malignant disease at the time of blood collection.
• Exposure: Asbestos exposure was not studied. The factors examined as possible predictors of positive mesothelin and calretinin tests were age, smoking status, 11 diseases, a cancer diagnosis after blood sampling, five types of medication, and 36 laboratory blood measures.
• Main results:
  • Among the 569 cancer-free men, 24 (4.2%) had mesothelin at or above 1.5 nM and 34 (6.0%) had calretinin at or above 1.0 ng/mL. The article gives specificities of 95.8% (95% CI 93.8% to 97.2%) for mesothelin and 94.0% (95% CI 91.7% to 95.7%) for calretinin.
  • Five men had both markers raised, giving a specificity of 99.1% (95% CI 97.9% to 99.7%) for the two markers combined.
  • In univariate models, cystatin C above the standard value had a prevalence odds ratio of 20.8 (95% CI 8.48 to 50.8) for positive mesothelin and 3.48 (95% CI 1.34 to 9.02) for positive calretinin.
  • In multiple models for positive mesothelin, the prevalence odds ratios were 11.0 (95% CI 4.02 to 30.0) for cystatin C, 8.41 (95% CI 1.07 to 66.0) for hypertension, and 1.08 (95% CI 1.00 to 1.17) for age.
  • In multiple models for positive calretinin, the prevalence odds ratios were 4.03 (95% CI 1.49 to 10.9) for cystatin C, 4.98 (95% CI 1.51 to 16.5) for cancer diagnosed after blood collection, and 5.19 (95% CI 1.54 to 17.4) for bronchial asthma.
  • Hypertension was not associated with positive calretinin (prevalence odds ratio 1.05, 95% CI 0.49 to 2.27).
  • Cancer was diagnosed in 20 participants after blood collection, 9 of them within 12 months.
• The authors' conclusion: The authors concluded that calretinin might be a useful adjunct to mesothelin for the early detection of mesothelioma, raising the specificity of the two-marker panel to 99.1% (95% CI 97.9% to 99.7%).
• Limitations the authors state:
  • Because both markers had high specificities, the analyses of predictors of false-positive tests were based on small numbers.
  • The men came from the general population, not from a cohort of asbestos workers, who have a higher prevalence of asbestosis.
  • The authors stated that specificity in asbestos-exposed workers, including those with asbestosis, is likely lower.
  • Only men were studied, so possible differences between men and women could not be investigated.
  • The findings on bronchitis and bronchial asthma rested on few men: 11 with bronchitis and 18 with bronchial asthma.

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: Calretinin, Mesothelin, Mesothelioma, Cohort Study.

Related studies

• Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine — S. Casjens, G. Johnen, et al. (2021)
• Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers — G. Johnen, K. Burek, et al. (2018)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis — C. Jiménez-Ramírez, D. Gilbert Weber, et al. (2022)
• Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population — G. Aguilar-Madrid, B. Pesch, et al. (2018)

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