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

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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.

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Acknowledgements

The authors owe their thanks to all patients with MPM (who died from a preventable disease), and to all controls that kindly participated in the study, specially to the community of San Pedro Barrientos, Tlalnepantla de Baz, State of Mexico and to retirees and authorities of the National Institute of Older Adults (INAPAM), Government of Mexico City, and thanks to Claudia Madrigal Esquivel MD who helped with patient recruitment.

Funding

This study was funded by Fondo de Investigación de Salud. FIS-IMSS-G11-935 del 2011–2013; Consejo Nacional de Ciencia y Tecnología. CONACYT. FONDO SECTORIAL SALUD-2012-01-181492 del 2012 al 2016; CONACYT-BMBF- Fondo de Cooperación Internacional (México-Alemania) No. 207978 del 2015–2017, and Bundesministerium für Bildung und Forschung (BMBF), grant 01DN15002.

Author information

Authors and Affiliations

  1. Department of Toxicology, Center for Research and Advanced Studies of National Polytechnic Institute, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, 07360, Mexico City, Mexico

    Carmina Jiménez-Ramírez, Luz M. Del Razo, Emma S. Calderón-Aranda & Leonor Concepción Acosta-Saavedra

  2. Occupational Health Research Unit, Siglo XXI National Medical Center (CMNSXXI), Mexican Institute of Social Security (IMSS), Av. Cuauhtémoc 330, Col. Doctores, 06720, México, México

    Carmina Jiménez-Ramírez, Cuauhtémoc Arturo Juárez-Pérez & Alejandro Cabello-López

  3. Clinical Analysis Laboratory, Traumatology Hospital “Dr. Victorio De La Fuente Narváez”. High Speciality Medical Unit (UMAE), Mexican Institute of Social Security (IMSS), Av. Colector 15 s/n Esq. Av. Instituto Politécnico Nacional, Col. Magdalena de las Salinas, 07760, Mexico City, Mexico

    Carmina Jiménez-Ramírez

  4. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Swaantje Casjens, Irina Raiko, Dirk Taeger, Hans-Peter Rihs, Daniel Gilbert Weber, Beate Pesch, Katarzyna Burek, Thomas Brüning & Georg Johnen

  5. Pneumology Service of the General Hospital, La Raza Medical Center, Mexican Institute of Social Security (IMSS), Paseo de las Jacarandas s/n, Col. La Raza, 02990, Mexico City, Mexico

    María Dolores Ochoa-Vázquez

  6. Clinical Research, National Institute of Respiratory Diseases (INER), Calzada de Tlalpan 4502, Col. Belisario Domínguez, Sección 16, 14080, Mexico City, Mexico

    Luis Torre-Bouscoulet & José Rogelio Pérez-Padilla

  7. Thorax Service, Oncology Hospital. High Speciality Medical Unit (UMAE), Siglo XXI National Medical Center (CMNSXXI), Mexican Institute of Social Security (IMSS), Av. Cuauhténmoc 330, Col. Doctores, 06720, Mexico City, Mexico

    Erik Marco García-Bazan

  8. Research and Graduate Division, Claustro Universitario de Chihuahua, Av. División del Norte No 3104 Col. Altavista, C. P. 31200, Chihuahua, Mexico

    Guadalupe Aguilar-Madrid

  9. Faculty of Medicine, Public Health Department, National Autonomous University of Mexico (UNAM), Av. Universidad 3000, Ciudad Universitaria, 04510, Mexico City, Mexico

    Guadalupe Aguilar-Madrid

Authors
  1. Carmina Jiménez-Ramírez
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  2. Swaantje Casjens
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  3. Cuauhtémoc Arturo Juárez-Pérez
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  4. Irina Raiko
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  5. Luz M. Del Razo
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  6. Dirk Taeger
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  7. Emma S. Calderón-Aranda
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  8. Hans-Peter Rihs
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  9. Leonor Concepción Acosta-Saavedra
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  10. Daniel Gilbert Weber
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  11. Alejandro Cabello-López
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  12. Beate Pesch
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  13. María Dolores Ochoa-Vázquez
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  14. Katarzyna Burek
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  15. Luis Torre-Bouscoulet
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  16. José Rogelio Pérez-Padilla
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  17. Erik Marco García-Bazan
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  18. Thomas Brüning
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  19. Georg Johnen
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  20. Guadalupe Aguilar-Madrid
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Contributions

CJR collected data, performed assays, analyzed data, and participated in writing the manuscript; SC analyzed data and participated in writing of the manuscript; IR performed assays and analyzed data; CAJP, LMDR, DT, ESCA, HPR, LCAS, DGW, ACL, BP, MDOV, KB, LTB, JRPP, EMGB, and TB contributed their critical opinion in the manuscript; GAM and GJ carried out the conception and design of the study, supervised the work, analyzed data, and participated in the writing of the manuscript.

Corresponding authors

Correspondence to Georg Johnen or Guadalupe Aguilar-Madrid.

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Conflict of interest

The IPA has received calretinin kits for a reduced price from DLD. Otherwise, none of the authors has any conflict of interest to declare in relation to this work.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Guadalupe Aguilar-Madrid is the first corresponding author and Georg Johnen is the second corresponding author.

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Jiménez-Ramírez, C., Casjens, S., Juárez-Pérez, C.A. et al. Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma. Lung 197, 641–649 (2019). https://doi.org/10.1007/s00408-019-00244-1

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