Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis

Our plain-English summary of Combination of MiR-103a-3p and mesothelin improves the biomarker performance of malignant mesothelioma diagnosis, by D.G. Weber, S. Casjens, G. Johnen, et al (PloS One, 2014).

The study

• Authors: D.G. Weber, S. Casjens, G. Johnen, O. Bryk, I. Raiko, B. Pesch, J. Kollmeier, T.T. Bauer, T. Brüning
• Journal: PloS One
• Published: 2014;9(12):e114483
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma.

Methods/principal Findings: Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were calculated.

Conclusions/significance: The results of this study show that the combination of mesothelin and miR-103a-3p improves the diagnostic performance of individual blood-based biomarker to detect malignant mesothelioma. The obtained results indicate that the use of biomarkers of different molecular classes might be a reasonable approach to assemble a biomarker panel.

In plain English

This German study tested whether combining two blood tests could better tell men with malignant mesothelioma apart from men who had been exposed to asbestos and did not have the disease. The authors measured a protein, mesothelin, in the liquid part of the blood (plasma). They also measured a small RNA molecule, miR-103a-3p, in the blood cells. Samples came from 43 male mesothelioma patients and 52 male asbestos-exposed controls. Across all subjects, the combined test picked up 86% of patients (sensitivity) and correctly identified 85% of controls as negative (specificity). Mesothelin alone gave 60% and 92%, and miR-103a-3p alone gave 86% and 63%. The combination missed four of the five sarcomatoid cases. With those five cases left out, the combination reached 95% sensitivity and 81% specificity. Repeating the analysis on 1,000 resampled data sets gave similar figures. The authors concluded that combining markers, especially markers of different molecular types, improved diagnostic performance. They noted that their study groups were relatively small and that it might be reasonable to test the combination in larger groups.

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: diagnostic biomarker study comparing mesothelioma patients with asbestos-exposed controls (case-control comparison using ROC analysis)
• Who was studied: 43 male mesothelioma patients (28 epithelioid, 6 biphasic, 5 sarcomatoid, 4 subtype not specified) and 52 male controls formerly exposed to asbestos. Participants were recruited at the HELIOS Clinic Emil von Behring in Berlin, Germany, and at medical practices taking part in the MoMar study. Median age was 72 for cases and 73 for controls. Study dates are not given.
• Exposure: The controls were formerly exposed to asbestos; no fiber types, jobs or doses are given. What was measured: mesothelin in plasma and miR-103a-3p in the cellular fraction of blood.
• Main results:
  • Median mesothelin was 1.96 nmol/l in mesothelioma cases and 0.93 nmol/l in controls. Median miR-103a-3p level was 294.3 in cases and 1020.7 in controls. Both differences were statistically significant (p less than 0.001).
  • All subjects, cut-off by maximum Youden's index: mesothelin alone gave 60% sensitivity and 92% specificity; miR-103a-3p alone gave 86% sensitivity and 63% specificity.
  • All subjects: the combination of mesothelin and miR-103a-3p gave 86% sensitivity and 85% specificity.
  • The combination tested four of the five sarcomatoid mesothelioma cases false-negative, but only one biphasic and one epithelioid case. Sarcomatoid cases had an odds ratio of 72 (95% CI 5; 982) of testing false-negative.
  • Excluding the five sarcomatoid cases: mesothelin alone gave 74% sensitivity and 85% specificity, miR-103a-3p alone gave 89% and 63%, and the combination gave 95% sensitivity and 81% specificity.
  • Area under the curve for all subjects was 0.81 for mesothelin, 0.76 for miR-103a-3p and 0.90 for the combination. Without sarcomatoid cases it was 0.85, 0.78 and 0.93.
  • With the cut-off set at a 4% false-positive rate (two false-positive controls), the combination's sensitivity was 65% for all subjects and 74% for subjects without sarcomatoid mesothelioma.
  • Bootstrap analysis (1,000 resamples) gave similar sensitivities and specificities for the combination. For all subjects at maximum Youden's index, sensitivity was 84% (95% CI 64; 96) and specificity was 87% (95% CI 71; 98).
• The authors' conclusion: The authors concluded that combining mesothelin and miR-103a-3p improved diagnostic performance. They wrote that their results support using combinations of biomarkers rather than single biomarkers, especially markers from different molecular classes.
• Limitations the authors state:
  • The results are based on relatively small study groups; the authors suggest testing the combination in larger groups.
  • Because miR-103a-3p was measured in blood cells, changes in its level may reflect an indirect effect, such as an immune response to the tumor.
  • An influence of hypertension on mesothelin levels cannot be ruled out. Influencing factors need evaluation in a sufficiently large group of healthy subjects.

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: Mesothelin, Biomarker, Malignant Mesothelioma, Mesothelioma, Epithelioid, Biphasic Mesothelioma.

Related studies

• 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 — C. Jiménez-Ramírez, D. Gilbert Weber, et al. (2022)
• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Mesothelin, Calretinin, and Megakaryocyte Potentiating Factor as Biomarkers of Malignant Pleural Mesothelioma — C. Jiménez-Ramírez, S. Casjens, et al. (2019)
• 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)
• Combination of mesothelin and CEA significantly improves the differentiation between malignant pleural mesothelioma, benign asbestos disease, and lung cancer — T. Muley, H. Dienemann, et al. (2013)
• A recombinant polypeptide of the megakaryocyte potentiating factor is a potential biomarker in plasma for the detection of mesothelioma — I. Raiko, H.P. Rihs, et al. (2017)

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