Does CA125 binding to mesothelin impact the detection of malignant mesothelioma?

Our plain-English summary of Does CA125 binding to mesothelin impact the detection of malignant mesothelioma?, by J. Creaney, I.M. Dick, H. Dare, et al (Lung Cancer, 2013).

The study

• Authors: J. Creaney, I.M. Dick, H. Dare, Y. Demelker, A.K. Nowak, A.W. Musk, B.W. Robinson
• Journal: Lung Cancer
• Published: 2013;80(1):39-44
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The biomarker mesothelin is a useful diagnostic tool in malignant mesothelioma (MM) patients. It has high specificity but a sensitivity of only 50%. As mesothelin binds CA125, and as CA125 is often elevated in MM, we asked whether this binding affected measurable mesothelin levels in a relevant clinical setting. Mesothelin and CA125 concentrations were measured in the serum of 41 patients with MM. An assay was developed to detect mesothelin bound to CA125. Mesothelin was demonstrated to be bound by CA125 in 9 of 41 MM patients. This binding could be broken by the addition of sodium dodecyl sulphate and diethylenetriaminepenta acetic acid (DTPA) to the samples, however this did not lead to any change in the mesothelin level measured. We therefore conclude that binding of mesothelin to CA125 does not alter the measurement of mesothelin for the detection of MM.

Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

In plain English

This laboratory study from Perth, Western Australia, asked whether CA125, a protein that can attach to the blood marker mesothelin, interferes with mesothelin tests for malignant mesothelioma. The authors measured both markers in blood serum from 41 patients with malignant mesothelioma. They also developed a test for mesothelin bound to CA125. Bound mesothelin was found in 9 of the 41 patients. All nine had CA125 above 35 U/mL and mesothelin above 4 nM, but four other patients with similar levels showed no binding. In laboratory mixtures, adding 40 U of CA125 significantly lowered measurable mesothelin at 8 nM and 32 nM. In serum from 8 patients, the chemicals DTPA and SDS removed detectable binding without significantly changing measured mesothelin. The authors noted that the chemicals may have altered detection rather than the binding itself. Patients with bound mesothelin had a median survival of 4.5 months, compared with 23 months for those without (p less than 0.001). The authors concluded that this binding does not prevent measurement of mesothelin in most clinical situations. They noted that the sample size was limited.

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: Laboratory biomarker study using stored serum samples from patients with malignant mesothelioma, with test-tube experiments and a survival analysis
• Who was studied: 41 patients with malignant mesothelioma who presented to respiratory clinics at Sir Charles Gairdner Hospital or Hollywood Specialist Centre in Perth, Western Australia. Patients with raised serum creatinine (reduced kidney function) were excluded. Collection dates are not given.
• Exposure: No asbestos exposure was assessed. The study measured blood levels of the markers mesothelin and CA125, and mesothelin bound to CA125.
• Main results:
  • Among the 41 patients, CA125 was above the normal limit of 35 U/mL in 18. Mesothelin was above 2.5 nM in 29.
  • CA125 was found bound to mesothelin in the serum of 9 of the 41 patients.
  • All nine patients with binding had CA125 above 35 U/mL and mesothelin above 4 nM. Four other patients with similar levels had no detectable binding.
  • In laboratory mixtures, adding 40 U of CA125 significantly reduced detectable mesothelin at 8 nM and 32 nM of mesothelin. Smaller amounts of CA125 (4 U) or of mesothelin (2 nM) showed no significant difference.
  • In serum from 8 patients, adding DTPA and SDS disrupted the binding of mesothelin and CA125 as observed in the assay. The authors noted elsewhere that this may reflect altered detection rather than a broken interaction.
  • In those same 8 patient samples, measured mesothelin did not change significantly after DTPA and SDS treatment.
  • None of the other treatments tried produced a significant increase in measured mesothelin after the binding was disrupted.
  • Patients with CA125 bound to mesothelin had a median survival of 4.5 months, compared with 23 months for patients without binding (p < 0.001). At censoring, 34 of the 41 patients had died.
  • No statistically significant survival difference was seen when patients were split by serum mesothelin status or by CA125 status.
  • In single-marker analysis, the concentration of each marker was linked to survival. Hazard ratios were 1.58 (1.08–2.32) for mesothelin, 1.42 (1.04–1.95) for CA125, and 1.50 (1.10–2.07) for bound CA125–mesothelin.
  • In multivariate analysis, mesothelin concentration was an independent indicator of survival. CA125 and bound mesothelin–CA125 supplied overlapping information.
• The authors' conclusion: The authors concluded that, although binding of mesothelin to CA125 was shown in patient samples, it does not prevent measurement of mesothelin in most clinical situations, particularly for early detection of disease.
• Limitations the authors state:
  • The authors noted that the sample size was limited, in the context of the survival finding.
  • The authors noted that DTPA and SDS treatment may have disrupted the detection of the binding without actually breaking the binding itself.

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, Malignant Mesothelioma, Biomarker.

Related studies

• Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma — J. Creaney, I. van Bruggen, et al. (2007)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• 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)
• Plasma versus serum levels of osteopontin and mesothelin in patients with malignant mesothelioma--which is best? — J. Creaney, D. Yeoman, et al. (2011)
• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)
• Pleural fluid mesothelin as an adjunct to the diagnosis of pleural malignant mesothelioma — J. Creaney, A. Segal, et al. (2014)

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