International Journal of Medical Sciences

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23 October 2018

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Int J Med Sci 2018; 15(9):883-891. doi:10.7150/ijms.23939

Research Paper

Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population

Guadalupe Aguilar-Madrid1*✉, Beate Pesch2*, Emma S Calderón-Aranda3, Katarzyna Burek2, Carmina Jiménez-Ramírez1,4, Cuauhtémoc Arturo Juárez-Pérez1, María Dolores Ochoa-Vázquez5, Luis Torre-Bouscoulet6, Leonor Concepción Acosta-Saavedra3, Isabel Sada-Ovalle7, Jorge García-Figueroa7, Isabel Alvarado-Cabrero8, Patricia Castillo-González9, Alejandra Renata Báez-Saldaña9, José Rogelio Pérez-Padilla10, Juvencio Osnaya-Juárez5, Rosa María Rivera-Rosales11, Eric Marco García-Bazán12, Yolanda Lizbeth Bautista-Aragón13, Elimelec Lazcano-Hernandez12, Daniel Alejandro Munguía-Canales14, Luis Marcelo Argote-Greene15, Dirk Taeger2, Daniel Gilbert Weber2, Swaantje Casjens2, Irina Raiko2, Thomas Brüning2, Georg Johnen2✉

1. Research Unit Health at Work, XXI Century National Medical Center (CMNSXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico
2. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany
3. Department of Toxicology, Center for Research and Advanced Studies, CINVESTAV, Mexico City, Mexico
4. Clinical Analysis Laboratory, Traumatology Hospital “Dr. Victorio De la Fuente Narvaez”, IMSS, Mexico City, Mexico
5. Pneumology Service of the General Hospital, Medical Center La Raza, IMSS, Mexico City, Mexico
6. Clinical Research, National Institute of Respiratory Diseases (INER), Mexico City, Mexico
7. Integrative Immunology Laboratory, INER, Mexico City, Mexico
8. Service Pathology, High Specialty Medical Unit (UMAE), Oncology Hospital, CMNSXXI, IMSS, Mexico City, Mexico
9. Clinical Oncology Pneumology Service, INER, Mexico City, Mexico
10. Research Department, INER, Mexico City, Mexico
11. Department of Pathology, INER, Mexico City, Mexico
12. Thorax Service, Oncology Hospital, High Specialty Medical Unit (UMAE), CMNSXXI, IMSS, Mexico City, Mexico
13. Medical Oncology, Oncology Hospital, High Specialty Medical Unit (UMAE), CMNSXXI, IMSS, Mexico City, Mexico
14. Service Chest Surgery, Hospital Cardiology, CMNSXXI, IMSS, Mexico City, Mexico
15. Thoracic Surgery, Case Western Reserve University Hospitals of Cleveland, USA
* These authors contributed equally to this work

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.

Keywords: mesothelioma, mesothelin, calretinin, diagnostic marker, asbestos.

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How to cite this article:
Aguilar-Madrid G, Pesch B, Calderón-Aranda ES, Burek K, Jiménez-Ramírez C, Juárez-Pérez CA, Ochoa-Vázquez MD, Torre-Bouscoulet L, Acosta-Saavedra LC, Sada-Ovalle I, García-Figueroa J, Alvarado-Cabrero I, Castillo-González P, Báez-Saldaña AR, Pérez-Padilla JR, Osnaya-Juárez J, Rivera-Rosales RM, García-Bazán EM, Bautista-Aragón YL, Lazcano-Hernandez E, Munguía-Canales DA, Argote-Greene LM, Taeger D, Weber DG, Casjens S, Raiko I, Brüning T, Johnen G. Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population. Int J Med Sci 2018; 15(9):883-891. doi:10.7150/ijms.23939. Available from http://www.medsci.org/v15p0883.htm