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

Our plain-English summary of 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, by C. Jiménez-Ramírez, D. Gilbert Weber, G. Aguilar-Madrid, et al (PloS One, 2022).

The study

• Authors: C. Jiménez-Ramírez, D. Gilbert Weber, G. Aguilar-Madrid, A. Brik, C.A. Juárez-Pérez, S. Casjens, I. Raiko, T. Brüning, G. Johnen, A. Cabello-López
• Journal: PloS One
• Published: 2022;17(10):e0275936
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This case-control study from Mexico tested whether miR-103a-3p, a small RNA molecule measured in white blood cells (leukocytes), improved blood testing for malignant pleural mesothelioma when added to two blood proteins, mesothelin and calretinin. It included 108 people with confirmed mesothelioma and 218 controls matched by sex and age. Most people in both groups had past occupational or environmental asbestos exposure. Median miR-103a-3p levels were lower in cases than in controls (217.52 vs 298.17). This difference was marginally significant in men (p = 0.05) but not in women. At fixed specificities of 95.5% in men and 97.4% in women, miR-103a-3p alone detected 4.4% of male cases and none of the female cases. Mesothelin and calretinin together detected 80.9% of male cases and 83.3% of female cases, and adding miR-103a-3p did not raise these figures. The authors concluded that adding miR-103a-3p did not improve diagnosis. They noted that metabolic conditions were assessed only by questionnaire or indirectly, and that results could not be compared by tumor subtype.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-control study of diagnostic blood biomarkers. Mesothelioma cases and controls were matched by sex and age.
• Who was studied: 108 malignant pleural mesothelioma cases (90 men, 18 women) and 218 controls (179 men, 39 women), median age 62 in both groups, in Mexico. Cases attended the Mexican Social Security Institute (IMSS) or the National Institute of Respiratory Diseases (INER) in Mexico City and had mesothelioma confirmed by immunohistochemistry. Controls came from a retiree registry (SINDO) and an elderly population registry (INAPAM). 82 cases and 212 controls came from the authors' earlier study.
• Exposure: Former asbestos exposure, occupational or environmental, was recorded for 96.3% of cases (104) and 91.3% of controls (199). Fiber types were not specified. The markers measured were miR-103a-3p in leukocytes (by quantitative real-time PCR) and mesothelin and calretinin in plasma (by ELISA).
• Main results:
  • Median miR-103a-3p was 217.52 in cases and 298.17 in controls. The difference was marginally significant in men (p = 0.05) but not in women.
  • Used alone, miR-103a-3p performed poorly. The area under the curve was 0.426 (95% CI 0.355 to 0.497) in men and 0.437 (95% CI 0.284 to 0.589) in women. Sensitivity was 4.4% in men (at 95.5% specificity) and 0% in women (at 97.4% specificity).
  • In men, at 95.5% specificity:
• mesothelin had an area under the curve of 0.894 (95% CI 0.847 to 0.941) and a sensitivity of 72.2%;
• calretinin had an area under the curve of 0.931 (95% CI 0.889 to 0.972) and a sensitivity of 80.9%.
  • Mesothelin and calretinin combined reached a sensitivity of 80.9% in men (95.5% specificity) and 83.3% in women (97.4% specificity). Adding miR-103a-3p did not increase sensitivity.
  • Median plasma mesothelin was 2.34 nmol/L in cases and 0.55 nmol/L in controls.
  • Median plasma calretinin was 1.52 ng/mL in cases and 0.13 ng/mL in controls.
  • Among controls, miR-103a-3p differed significantly by age: 203.15 in those aged 60 or younger vs 379.03 in those over 60.
  • In male controls, years of occupational asbestos exposure were negatively but weakly correlated with miR-103a-3p (rho = -0.128, p = 0.029).
  • Positive correlations between miR-103a-3p and environmental asbestos exposure were seen among women.
  • In men split by age, the sensitivity of miR-103a-3p alone doubled in a subgroup. Even so, adding it to mesothelin and calretinin did not improve performance.
• The authors' conclusion: The authors concluded that adding miR-103a-3p to mesothelin and calretinin did not improve the diagnostic performance for malignant pleural mesothelioma.
• Limitations the authors state:
  • Results could not be compared by histological subtype because there were too few biphasic and sarcomatoid cases.
  • Metabolic conditions were assessed only by questionnaire or indirectly through biochemical tests.
  • Blood pressure information came from a questionnaire, not from measurement.
  • No markers of early kidney damage were measured.
  • The authors suggested that the failure of miR-103a-3p to separate cases from controls may reflect the sample type used: isolated leukocytes rather than the whole cellular fraction of blood.
  • The authors said miR-103a-3p needs to be evaluated in a larger number of women.
  • miR-103a-3p was measured in two batches, in 2015 and 2021, on different PCR systems. The authors noted group differences between the years but found the 2021 values within the 2015 range.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelin, Calretinin, Pleural Mesothelioma, Asbestos Exposure.

Related studies

• Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis — D.G. Weber, S. Casjens, et al. (2014)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• Calretinin as a blood-based biomarker for mesothelioma — G. Johnen, K. Gawrych, et al. (2017)
• Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers — G. Johnen, K. Burek, et al. (2018)
• Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population — G. Aguilar-Madrid, B. Pesch, et al. (2018)
• Identification of miRNA-103 in the cellular fraction of human peripheral blood as a potential biomarker for malignant mesothelioma--a pilot study — D.G. Weber, G. Johnen, et al. (2012)

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