Carmina Jiménez-Ramírez1,2,3, Swaantje Casjens4, Cuauhtémoc Arturo Juárez-Pérez2, Irina Raiko4, Luz M Del Razo1, Dirk Taeger4, Emma S Calderón-Aranda1, Hans-Peter Rihs4, Leonor Concepción Acosta-Saavedra1, Daniel Gilbert Weber4, Alejandro Cabello-López2, Beate Pesch4, María Dolores Ochoa-Vázquez5, Katarzyna Burek4, Luis Torre-Bouscoulet6, José Rogelio Pérez-Padilla6, Erik Marco García-Bazan7, Thomas Brüning4, Georg Johnen8, Guadalupe Aguilar-Madrid9,10. 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. 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. 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. 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. 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. 6. Clinical Research, National Institute of Respiratory Diseases (INER), Calzada de Tlalpan 4502, Col. Belisario Domínguez, Sección 16, 14080, Mexico City, Mexico. 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. 8. 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. johnen@ipa-dguv.de. 9. Research and Graduate Division, Claustro Universitario de Chihuahua, Av. División del Norte No 3104 Col. Altavista, C. P. 31200, Chihuahua, Mexico. gpeaguilarm@gmail.com. 10. Faculty of Medicine, Public Health Department, National Autonomous University of Mexico (UNAM), Av. Universidad 3000, Ciudad Universitaria, 04510, Mexico City, Mexico. gpeaguilarm@gmail.com.
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.
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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