Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma

Our plain-English summary of Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma, by J. Creaney, I. van Bruggen, M. Hof, et al (Chest, 2007).

The study

• Authors: J. Creaney, I. van Bruggen, M. Hof, A. Segal, A.W. Musk, N. de Klerk, N. Horick, S.J. Skates, B.W. Robinson
• Journal: Chest
• Published: 2007;132(4):1239-46
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma is an aggressive, uniformly fatal tumor. Serum markers would be useful for the diagnosis of this disease. One potential marker is mesothelin. The purpose of this study was to study the mesothelin biomarker in a large patient cohort and to determine if another biomarker, CA125, improves on the sensitivity of mesothelin in the diagnosis of mesothelioma.

Methods: Serum levels of mesothelin and CA125 were determined by commercially available assays in 117 samples obtained at diagnosis from patients with pleural malignant mesothelioma, 33 healthy, asbestos-exposed individuals, 53 patients with asbestos-related lung or pleural disease, and 30 patients presenting with benign pleural effusions. Cross-validated sensitivities were determined, and receiver operator characteristic curves were generated to compare the diagnostic accuracy of the biomarkers.

Results: CA125 had a cross-validated sensitivity of 27% for mesothelioma patients at a specificity of 95% relative to asbestos-exposed individuals, or 50% relative to individuals with benign pleural effusions. Mesothelin had a cross-validated sensitivity of 52% for mesothelioma patients, at a sensitivity of 95% relative to individuals with benign lung or pleural disease. CA125 and mesothelin levels were discordant in > 50% of mesothelioma patients. Combining the data from the two biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone.

Conclusion: Combining mesothelin and CA125 data does not improve the sensitivity of mesothelioma diagnosis over mesothelin alone. The use of both markers potentially increases the number of patients who can be monitored.

In plain English

This study, carried out at a research centre in Western Australia, tested whether two blood markers, mesothelin and CA125, could help diagnose pleural malignant mesothelioma. The authors measured both markers in blood taken around the time of diagnosis from 117 patients with pleural mesothelioma. They compared the results with blood from 33 healthy asbestos-exposed people, 53 people with asbestosis (some also with pleural plaques), and 30 patients with non-cancerous pleural effusions. Mesothelin was raised in 56 of 117 mesothelioma patients (48%), in 1 of 53 people with asbestos-related disease, in none of the 33 healthy exposed people, and in 1 of 30 effusion patients. CA125 was raised in 49 of 117 mesothelioma patients (42%), but also in 16 of 30 effusion patients and 2 of 33 healthy exposed people. The two markers were often raised in different patients. Combining them did not perform significantly better than mesothelin alone. The authors concluded that adding CA125 does not improve on mesothelin and that CA125 alone is unlikely to be useful for screening. They noted that they had only four blood samples taken before diagnosis.

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: Diagnostic biomarker study comparing serum mesothelin and CA125 levels in mesothelioma patients with control groups, using ROC curves and cross-validated sensitivity, plus immunohistochemical staining of tumor tissue and effusions
• Who was studied: 117 patients with pleural malignant mesothelioma, sampled within 6 weeks before or after diagnosis. Controls were 33 healthy asbestos-exposed individuals, 53 patients with benign asbestos-related disease (14 with asbestosis, 39 with asbestosis and pleural plaques) and 30 patients with benign pleural effusions. Four additional premorbid samples came from people who developed mesothelioma 1 to 7 years later. The work was done at the National Research Centre for Asbestos Related Diseases, Western Australia. Dates are not given.
• Exposure: This was not a study of exposure levels. Control groups had a history of asbestos exposure, with no fiber types or doses reported. The measures studied were serum mesothelin (Mesomark assay, manufacturer cut-off 2.5 nmol/L) and serum CA125 (Immulite assay, manufacturer cut-off 21 U/mL).
• Main results:
  • Mesothelin was elevated at diagnosis in 56 of 117 mesothelioma patients (48%).
  • Mesothelin was elevated in 1 of 53 people with benign asbestos-related disease, in none of the 33 healthy asbestos-exposed individuals, and in 1 of 30 patients with benign pleural effusions.
  • CA125 was elevated at diagnosis in 49 of 117 mesothelioma patients (42%).
  • CA125 was also elevated in 16 of 30 patients with benign pleural effusions, in 7 of 53 with benign asbestos-related disease, and in 2 of 33 healthy asbestos-exposed individuals.
  • The two markers were often raised in different mesothelioma patients: 18% were positive for both, 30% for mesothelin only, 24% for CA125 only, and 28% for neither.
  • In distinguishing mesothelioma patients from asbestos-exposed individuals with and without benign disease, the AUC was 0.790 (95% CI 0.729 to 0.851) for mesothelin, 0.687 (95% CI 0.614 to 0.759) for CA125, and 0.801 (95% CI 0.741 to 0.861) for the combined markers. The combined AUC was not significantly different from mesothelin alone.
  • In the cross-validated analysis at 95% specificity, sensitivity was 52% for mesothelin, 27% for CA125 and 44% for the combination. At 98% specificity it was 49%, 9% and 42% respectively.
  • Of four serum samples taken 1 to 7 years before mesothelioma developed, three were mesothelin positive and none had elevated CA125.
• The authors' conclusion: The authors concluded that combining mesothelin and CA125 does not improve the sensitivity of mesothelioma diagnosis over mesothelin alone. They also concluded that CA125 alone is unlikely to be useful for screening for mesothelioma.
• Limitations the authors state:
  • Only four premorbid (pre-diagnosis) mesothelioma samples could be studied.
  • Cross-validation reduces but does not completely eliminate overfitting of the sensitivity estimates.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Biomarker, Pleural Effusion.

Related studies

• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Mesothelin-family proteins and diagnosis of mesothelioma — B.W. Robinson, J. Creaney, et al. (2003)
• Sensitivity of urinary mesothelin in patients with malignant mesothelioma — J. Creaney, A.W. Musk, et al. (2010)
• Does CA125 binding to mesothelin impact the detection of malignant mesothelioma? — J. Creaney, I.M. Dick, et al. (2013)
• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure — J.A. Rodríguez Portal, E. Rodríguez Becerra, et al. (2009)

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