Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population

Our plain-English summary of Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population, by G. Aguilar-Madrid, B. Pesch, E.S. Calderón-Aranda, et al (International Journal of Medical Sciences, 2018).

The study

• Authors: G. Aguilar-Madrid, B. Pesch, E.S. Calderón-Aranda, K. Burek, C. Jiménez-Ramírez, C.A. Juárez-Pérez, M.D. Ochoa-Vázquez, L. Torre-Bouscoulet, L.C. Acosta-Saavedra, I. Sada-Ovalle, J. García-Figueroa, I. Alvarado-Cabrero, P. Castillo-González, A.R. Báez-Saldaña, J.R. Pérez-Padilla, J. Osnaya-Juárez, R.M. Rivera-Rosales, E.M. García-Bazán, Y.L. Bautista-Aragón, E. Lazcano-Hernandez, D.A. Munguía-Canales, L.M. Argote-Greene, D. Taeger, D.G. Weber, S. Casjens, I. Raiko, T. Brüning, G. Johnen
• Journal: International Journal of Medical Sciences
• Published: 2018;15(9):883-891
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Diagnosis of malignant pleural mesothelioma (MPM) remains a challenge, especially when resources in pathology are limited. The study aimed to evaluate cost-effective tumor markers to predict the probability of MPM in plasma samples in order to accelerate the diagnostic workup of the tissue of potential cases. Methods: We conducted a case-control study stratified by gender, which included 75 incident cases with MPM from three Mexican hospitals and 240 controls frequency-matched by age and year of blood drawing. Plasma samples were obtained to determine mesothelin, calretinin, and thrombomodulin using enzyme-linked immunosorbent assays (ELISAs). We estimated the performance of the markers based on the area under the curve (AUC) and predicted the probability of an MPM diagnosis of a potential case based on the marker concentrations. Results: Mesothelin and calretinin, but not thrombomodulin were significant predictors of a diagnosis of MPM with AUCs of 0.90 (95% CI: 0.85-0.95), 0.88 (95% CI: 0.82-0.94), and 0.51 (95% CI: 0.41-0.61) in males, respectively. For MPM diagnosis in men we estimated a true positive rate of 0.79 and a false positive rate of 0.11 for mesothelin. The corresponding figures for calretinin were 0.81 and 0.18, and for both markers combined 0.84 and 0.11, respectively. Conclusions: We developed prediction models based on plasma concentrations of mesothelin and calretinin to estimate the probability of an MPM diagnosis. Both markers showed a good performance and could be used to accelerate the diagnostic workup of tissue samples in Mexico.

In plain English

This case-control study in the Valley of Mexico (2012 to 2015) tested whether three blood proteins could help predict malignant pleural mesothelioma. It compared plasma from 75 newly diagnosed patients (63 men, 12 women) and 240 controls (172 men, 68 women). Among men, 93.7% of cases and 70.3% of controls were classed as ever exposed to asbestos at work. Mesothelin and calretinin levels were higher in cases than controls. Thrombomodulin levels did not differ significantly. In men, the area under the curve (how well a test separates cases from controls) was 0.90 (95% CI 0.85-0.95) for mesothelin and 0.88 (95% CI 0.82-0.94) for calretinin. At a 30% predicted probability, mesothelin flagged 79% of male cases and 11% of male controls. Both markers combined flagged 84% of male cases and 11% of male controls. The authors concluded that both markers performed well and could speed up examination of tissue samples in Mexico. They noted that results for women rest on only 12 cases. They said the markers need prospective validation before use in people without symptoms.

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) tumor markers, stratified by gender
• Who was studied: 75 incident malignant pleural mesothelioma cases (63 men, 12 women) from three Mexican referral hospitals and 240 controls (172 men, 68 women) matched by age and year of blood drawing, enrolled in the Valley of Mexico from January 2012 to April 2015
• Exposure: The study measured plasma mesothelin, calretinin and thrombomodulin. An industrial hygienist classed lifetime occupational asbestos exposure as ever or never from job histories. No fiber types were specified. Ever exposed: 93.7% of male cases and 70.3% of male controls; 33.3% of female cases and 17.7% of female controls.
• Main results:
  • Many men were classed as ever exposed to asbestos at work: 93.7% of male cases and 70.3% of male controls.
  • Median mesothelin in men was 2.21 nmol/l in cases and 0.58 nmol/l in controls (p less than 0.0001). In women it was 2.00 nmol/l in cases and 0.55 nmol/l in controls.
  • Median calretinin in men was 0.93 ng/ml in cases and below 0.07 ng/ml in controls (p less than 0.0001). In women it was 0.86 ng/ml in cases and below 0.22 ng/ml in controls.
  • Thrombomodulin did not differ significantly between cases and controls: 2.57 vs 2.30 ng/ml in men (p = 0.81) and 2.25 vs 2.05 ng/ml in women (p = 0.84).
  • Odds ratios for a mesothelioma diagnosis per unit increase of the log-transformed concentration: mesothelin 14.51 (95% CI 6.96-30.28) in men and 28.57 (95% CI 4.09-199.4) in women; calretinin 3.03 (95% CI 2.20-4.18) in men and 2.69 (95% CI 1.31-5.56) in women.
  • Area under the curve for mesothelin was 0.90 (95% CI 0.85-0.95) in men and 0.92 (95% CI 0.79-1.00) in women.
  • Area under the curve for calretinin was 0.88 (95% CI 0.82-0.94) in men and 0.77 (95% CI 0.61-0.93) in women.
  • At a 30% predicted probability, mesothelin alone gave true positive rates of 0.79 in men and 0.75 in women. The false positive rates were 0.11 in men and 0.03 in women.
  • In men at 30% probability, combining mesothelin and calretinin gave 84% true-positive and 11% false-positive decisions. Calretinin alone gave 81% and 18%.
  • In women, adding calretinin did not improve the performance of mesothelin.
• The authors' conclusion: The authors concluded that prediction models based on plasma mesothelin and calretinin performed well and could be used to accelerate the diagnostic workup of tissue samples in Mexico.
• Limitations the authors state:
  • The study had limited statistical power for women, with only 12 female cases.
  • Because of the case-control design and matching, the study could not estimate the effect of age and gender as risk factors.
  • Before the markers are used in people without symptoms, their ability to detect mesothelioma earlier must be validated in a prospective study.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Pathology, Tumor Marker, Case-Control Study, Mesothelin, Calretinin.

Related studies

• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• 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)
• Calretinin as a blood-based biomarker for mesothelioma — G. Johnen, K. Gawrych, et al. (2017)
• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• 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)
• Malignant Pleural Mesothelioma: Accuracy of CT Against Immunohistochemical Test Among the Mexican Population — R. Gopar-Nieto, G. Aguilar-Madrid, et al. (2015)

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