Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma

Our plain-English summary of Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma, by C. Jiménez-Ramírez, S. Casjens, C.A. Juárez-Pérez, et al (Lung, 2019).

The study

• Authors: C. Jiménez-Ramírez, S. Casjens, C.A. Juárez-Pérez, I. Raiko, L.M. Del Razo, D. Taeger, E.S. Calderón-Aranda, H.P. Rihs, L.C. Acosta-Saavedra, D.G. Weber, A. Cabello-López, B. Pesch, M.D. Ochoa-Vázquez, K. Burek, L. Torre-Bouscoulet, J.R. Pérez-Padilla, E.M. García-Bazan, T. Brüning, G. Johnen, G. Aguilar-Madrid
• Journal: Lung
• Published: 2019;197(5):641-649
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case-control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM.

Method: A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016.

Results: Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02-20.78) for mesothelin, 20.44 (95% CI 8.90-46.94) for calretinin, and 4.37 (95% CI 1.60-11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32-113.99), 17.89 (95% CI 3.93-81.49), and 2.77 (95% CI 0.47-16.21), respectively.

Conclusions: To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

In plain English

This case-control study in Mexico City and its metropolitan area measured three blood proteins: mesothelin, calretinin and megakaryocyte potentiating factor (MPF). The participants were 166 newly diagnosed patients with malignant pleural mesothelioma (128 men, 38 women) and 378 population controls of Mestizo-Mexican ethnicity, recruited from October 2011 to February 2016. Most cases and controls reported asbestos exposure at work or in their environment. All three proteins were higher in patients than in controls. With cut-offs set so that 95% of controls tested negative, calretinin alone detected 81.1% of male patients and mesothelin alone 78.9% of female patients. The best two-marker pairs did better, although the authors found no significant benefit from combining mesothelin with MPF. Calretinin plus MPF detected 84.3% of male patients, and mesothelin plus calretinin 86.8% of female patients. Adding a third marker gave no further gain. Calretinin levels in controls differed significantly by sex. The authors concluded that the panel performed well in this population, with high sensitivity and specificity. They noted that they did not ask about the reproductive system or record weight and height.

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: case-control study of blood (plasma) biomarkers for diagnosing malignant pleural mesothelioma
• Who was studied: 166 incident (newly diagnosed) cases of malignant pleural mesothelioma (128 men, 38 women) and 378 population controls (255 men, 123 women) of Mestizo-Mexican ethnicity, recruited in Mexico City and its metropolitan area from October 2011 to February 2016
• Exposure: The study measured plasma levels of mesothelin, calretinin and MPF by ELISA. Occupational and environmental asbestos exposure was reported for 124 (96.9%) male cases and 227 (89.0%) male controls, and for 34 (89.5%) female cases and 106 (86.2%) female controls. No fiber types are named.
• Main results:
  • Levels of all three markers differed statistically between cases and controls (p less than 0.001). For example, median mesothelin was 2.35 nmol/L in male cases and 0.56 nmol/L in male controls.
  • At a fixed specificity of 95%, the best single marker was calretinin in men (AUC 0.923; sensitivity 81.1%) and mesothelin in women (AUC 0.913; sensitivity 78.9%).
  • The best two-marker combination was calretinin plus MPF in men (AUC 0.938; sensitivity 84.3%) and mesothelin plus calretinin in women (AUC 0.947; sensitivity 86.8%).
  • Mesothelin and MPF were the most closely correlated pair (correlation 0.85 in males). The authors found no significant benefit from combining them.
  • Adding a third biomarker did not further improve performance. All three combined gave an AUC of 0.944 with 82% sensitivity in men, and an AUC of 0.937 with 87% sensitivity in women.
  • In men, adjusted odds ratios for being a case when a marker was above its cut-off were: mesothelin 7.92 (95% CI 3.02 to 20.78), calretinin 20.44 (95% CI 8.90 to 46.94) and MPF 4.37 (95% CI 1.60 to 11.94).
  • In women, the corresponding adjusted odds ratios were: mesothelin 28.89 (95% CI 7.32 to 113.99), calretinin 17.89 (95% CI 3.93 to 81.49) and MPF 2.77 (95% CI 0.47 to 16.21).
  • Calretinin levels in the control groups differed significantly between men and women.
  • Median levels of the three markers did not differ significantly by disease stage.
• The authors' conclusion: The authors concluded that the biomarker panel performed well in a Mestizo-Mexican population, with high sensitivity and specificity for diagnosing malignant pleural mesothelioma.
• Limitations the authors state:
  • The questionnaire did not ask about the reproductive system. The authors raised this while discussing a possible explanation for higher calretinin levels in female controls.
  • The weight and height of participants were not recorded.

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: Mesothelin, Calretinin, Biomarker, Pleural Mesothelioma, Case-Control Study.

Related studies

• Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population — G. Aguilar-Madrid, B. Pesch, et al. (2018)
• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)
• 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)
• 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)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor — K. Hollevoet, K. Nackaerts, et al. (2012)

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