MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study

Our plain-English summary of MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study, by P. Mozzoni, L. Ampollini, M. Goldoni, et al (Disease Markers, 2017).

The study

• Authors: P. Mozzoni, L. Ampollini, M. Goldoni, R. Alinovi, M. Tiseo, L. Gnetti, P. Carbognani, M. Rusca, A. Mutti, A. Percesepe, M. Corradi
• Journal: Disease Markers
• Published: 2017;2017:9645940
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression.

Aims: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients.

Methods: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients.

Conclusions: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

In plain English

This pilot study, from the University of Parma, Italy, measured four microRNAs (small gene-regulating molecules): miRNA-16, miRNA-17, miRNA-126 and miRNA-486. They were measured in blood plasma from 32 people with malignant pleural mesothelioma, 14 with asbestosis and 15 controls with other noncancerous lung diseases, and in stored tumor tissue from 24 of the mesothelioma patients. The article does not describe the patients' asbestos exposure. All four microRNAs were significantly lower in plasma of both the mesothelioma and asbestosis groups than in controls; no statistically significant difference was found between the two disease groups. For example, median relative miRNA-16 was 25.1 in mesothelioma patients, 22.1 in asbestosis patients and 128.0 in controls. In mesothelioma patients, plasma and tissue levels of miRNA-16, miRNA-17 and miRNA-486 were correlated. In single-factor analyses, higher miRNA-16 in plasma and tissue, and higher miRNA-486 in tissue, were associated with longer survival. The authors concluded that miRNA-16 may be a possible prognostic marker. They noted their sample was small and that a large multicenter study is needed.

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: Pilot biomarker study comparing patient groups (mesothelioma, asbestosis, noncancerous lung disease controls), with univariate survival analysis in the mesothelioma patients
• Who was studied: 32 patients with malignant pleural mesothelioma awaiting surgery (24 men, 8 women; 26 epithelioid, 6 biphasic; tumor tissue available for 24), 14 patients with asbestosis (8 men, 6 women), and 15 controls with other noncancerous pulmonary diseases (8 with nodules, 3 with bronchiectasis, 4 other). The authors are at the University of Parma, Italy. Recruitment dates are not given.
• Exposure: Asbestos exposure was not measured or described. Groups were defined by diagnosis, and no fiber types, jobs or doses are reported. The measured factors were plasma and tissue levels of miRNA-16, miRNA-17, miRNA-126 and miRNA-486, plus plasma VEGF.
• Main results:
  • Plasma miRNA-17 was significantly lower in mesothelioma and asbestosis patients than in controls. Median relative expression (interquartile range) was 2.9 (2.2 to 5.5) in the mesothelioma group, 2.1 (1.5 to 3.5) in the asbestosis group and 13.0 (6.1 to 19.7) in controls. No differences were detected between the mesothelioma and asbestosis groups.
  • Plasma miRNA-126 was lower in mesothelioma patients, at 1.3 (1.0 to 1.9), and in asbestosis patients, at 2.9 (1.6 to 4.3), than in controls, at 6.7 (5.5 to 8.3). The two disease groups were not statistically different.
  • Plasma miRNA-486 was significantly lower in mesothelioma patients, at 2.9 (1.0 to 8.4), and in asbestosis patients, at 1.7 (1.0 to 4.3), than in controls, at 14.9 (9.5 to 22.6). The two disease groups were not statistically different.
  • Plasma miRNA-16 was significantly lower in mesothelioma patients, at 25.1 (9.2 to 76.1), and in asbestosis patients, at 22.1 (10.7 to 29.9), than in controls, at 128.0 (84.5 to 190.7). No differences were detected between the two disease groups.
  • ROC curves were used to tell the combined mesothelioma and asbestosis patients apart from controls. Areas under the curve were 0.88 (95% CI 0.78 to 0.98) for miRNA-17, 0.95 (0.89 to 1.00) for miRNA-126, 0.88 (0.79 to 0.96) for miRNA-486 and 0.89 (0.81 to 0.97) for miRNA-16. The authors described the diagnostic power as always good.
  • In mesothelioma patients, plasma and tissue levels were correlated for miRNA-17 (r = 0.64), miRNA-486 (R = 0.66) and miRNA-16 (R = 0.59). No correlation was found for miRNA-126.
  • In mesothelioma patients, univariate Cox models showed that higher levels of three measures were associated with longer cumulative survival (hazard ratios below 1 per 1-unit increase in the logarithm). Plasma miRNA-16 had a hazard ratio of 0.35 (0.11 to 1.0), p = 0.05. Tissue miRNA-16 had a hazard ratio of 0.02 (0.001 to 0.42), p = 0.012. Tissue miRNA-486 had a hazard ratio of 0.24 (0.09 to 0.64), p = 0.005.
  • In the mesothelioma group only, miRNA-126 showed a significant but weak inverse correlation with plasma VEGF (R = -0.37). VEGF levels did not differ among the groups.
  • None of the microRNAs was related to tumor histology. miRNA-486 was lower in the biphasic type than in the epithelioid type, but this difference was not statistically significant.
• The authors' conclusion: The authors concluded that all four microRNA levels were decreased in patients with mesothelioma or asbestosis. In their view, this supports circulating microRNAs as a potential tool for asbestos-related diseases, and miRNA-16 as a possible prognostic marker in mesothelioma. They added that validation in a large multicenter project is required before routine clinical use.
• Limitations the authors state:
  • The authors stated that the sample size was small.
  • Only univariate survival models were run; the authors did not perform multivariate models at this stage.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker, Prognosis.

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