Biomarkers For Diagnosis Of Malignant Pleural Mesothelioma

Guadalupe AGUILAR-MADRID, Instituto Mexicano del Seguro Social. IMSS, Mexico
CALDERON-ARANDA E. 2 , JUAREZ-PEREZ C. 1 , JIMENEZ-RAMIREZ C. 3 , ACOSTA-SAAVEDRA L. 2 , OCHOA VAZQUEZ M. 4 , TORRE-BOUSCOULET L. 5 , SADA-OVALLE I. 6 , JOHNEN G. 7 , PESCH B. 8 , BRÜNING T. 9

1 Occupational Health Research Unit, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico
2 Toxicology Laboratory, Centro de Investigacion y Estudios Avanzados. CINVESTAV, Mexico City, Mexico
3 Clinical Analysis Laboratory, Hospital de Traumatología, Instituto Mexicano del Seguro Social, Mexico City, Mexico
4 Pneumology Service Hospital General. Centro Médico La Raza, Instituto Mexicano del Seguro Social, IMSS, Mexico City, Mexico
5 Department of Respiratory Physiology, Instituto Nacional de Enfermedades Respiratorias INER, Mexico City, Mexico
6 Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias. INER, Mexico City, Mexico
7 Head Center of Molecular Medicine Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA) Ruhr-University Boch
8 Center of Epidemiology. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA) Ruhr-University Boch
9 Director of Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA) Ruhr - University Boch

Aims. To determine the diagnostic performance of two plasma-biomarkers –mesothelin and calretinin – for the diagnosis of MPM, and set their cut off points in the population studied.
Methods. We carried out a case–control study of MPM in 652 insured by the Mexican Institute of Social Security, all Valley of Mexico residents, with 163 incident cases and 489 controls. Plasmatic levels of the biomarkers were measured in all participants by immunoassay sandwich-ELISA technique. Cases were confirmed through immunohistopathological examination. ROC curve analyses, and cut off points were established according to maximum sensitivity and specificity for each biomarker. Unconditional logistic regression models were built to calculate the probability of each biomarker to determine a case of MPM.
Results. Mesothelin AUC was 0.92 (CI;0.87-0.97) with the cut-off point at 0.84 nmol/L (sensitivity of 90.6%; specificity of 80.2%). The AUC of calretinin was 0.85 (CI;0.79-0.91) with the cut-off point at 0.23 ng/mL (sensitivity 83.7%; specificity 70%). The an unconditional logistic regression model was built, with each biomarker based on the cut off points; when mesothelin are >0.84 nmol/L, the OR=12.4 (CI; 5.3-28.5); when calretinin are >0.23ng/mL, the OR=9.4 (CI; 4.4-20.2) and occupational exposure the OR=3.9 (1.4-9.7) and  adjusting for age.
Conclusions. Our study provides evidence supporting the mesothelin and calretinin in plasma, can support the diagnosis of MPM. However, further studies to develop a panel of biomarkers are still needed.
Funding Source
Consejo Nacional de Ciencia y Tecnología. CONACYT-Mexico) No. 2012-01-181492 (2012-2016)
 Consejo Nacional de Ciencia y Tecnología. CONACYT (México) and Federal Ministry of Education and Research (BMBF-Germany) No. 207978. Collaborative research project Mexico-Germany ( 2015-2017)
Fondo de Investigacion en Salud del IMSS- G11-935 ( 2011-2013)