Assessment of miR-103a-3p in leukocytes-No diagnostic benefit in combination with the blood-based biomarkers mesothelin and calretinin for malignant pleural mesothelioma diagnosis

PLoS One. 2022 Oct 14;17(10):e0275936. doi: 10.1371/journal.pone.0275936. eCollection 2022.

Abstract

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asbestos* / adverse effects
  • Bilirubin
  • Biomarkers, Tumor / genetics
  • Calbindin 2 / genetics
  • Creatinine
  • Female
  • GPI-Linked Proteins / genetics
  • Glucose
  • Humans
  • Leukocytes / pathology
  • Lung Neoplasms* / pathology
  • Male
  • Mesothelin
  • Mesothelioma* / diagnosis
  • Mesothelioma* / genetics
  • Mesothelioma, Malignant*
  • MicroRNAs* / genetics
  • Middle Aged
  • Pleural Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • Calbindin 2
  • GPI-Linked Proteins
  • MicroRNAs
  • Asbestos
  • Creatinine
  • Glucose
  • Mesothelin
  • Bilirubin

Grant support

- Fondo de Investigación de Salud, FIS-IMSS-G11-935, in 2011-2013 (to GAM). - Consejo Nacional de Ciencia y Tecnología (CONACYT), FONDO SECTORIAL SALUD-2012-01-181492, in 2012-2016 (to GAM). - Bundesministerium für Bildung und Forschung (BMBF), 01DN15002, in 2015-2017 (to GJ) - CONACYT-BMBF-Fondo de Cooperación Internacional (México-Alemania), 207978, in 2015-2017 (to GAM). - Open Access Publication Fund of the Ruhr University Bochum, C01309, in 2022 (to GJ) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.