Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease

Our plain-English summary of Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease, by T. Cavalleri, L. Angelici, C. Favero, et al (PloS One, 2017).

The study

• Authors: T. Cavalleri, L. Angelici, C. Favero, L. Dioni, C. Mensi, C. Bareggi, A. Palleschi, A. Rimessi, D. Consonni, L. Bordini, A. Todaro, V. Bollati, A.C. Pesatori
• Journal: PloS One
• Published: 2017;12(5):e0176680
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE).

Methodology/principal Findings: We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87-1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13-1.13) and of 0.51 (95%CI 0.17-1.52) for miR-30e-3p.

Conclusions: This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.

In plain English

This Italian study measured small RNA molecules called microRNAs, carried in tiny particles (extracellular vesicles) in blood plasma. It compared 23 patients with malignant pleural mesothelioma with 19 cancer-free people who had documented past occupational asbestos exposure, all recruited in Milan between October 2013 and August 2014. Of 754 microRNAs screened, 435 were detectable. The top 20 were retested, and 16 were confirmed as lower in the mesothelioma patients. Combining two of them, miR-103a-3p and miR-30e-3p, separated the two groups with an area under the curve of 0.942 (95% CI 0.875 to 1.00), a sensitivity of 95.5% and a specificity of 80.0%. In the asbestos-exposed group, levels of these two microRNAs were not associated with years of exposure. Patients with levels above the median tended to survive longer, but this was not statistically significant. The authors concluded that their findings suggest a vesicle-based microRNA signature able to distinguish mesothelioma patients from asbestos-exposed people. They stated that the small number of subjects, and the lack of people with other chest diseases, prevent firm conclusions.

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 comparison of blood biomarkers (microRNAs in plasma extracellular vesicles): a screening step followed by a validation step, with survival follow-up of the mesothelioma patients
• Who was studied: 23 malignant pleural mesothelioma (MPM) patients from the Thoracic Surgery Unit, and 19 cancer-free subjects with documented past occupational asbestos exposure (PAE) in a clinical surveillance program at the Occupational Health Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, October 2013 to August 2014. MPM patients were followed to January 2016.
• Exposure: Lifetime asbestos exposure (occupational and environmental) assessed by a standardized questionnaire. Fiber types are not specified. Exposure was ascertained in 69.6% of MPM cases, and all 19 PAE subjects had definite occupational exposure. Mean years of exposure were 21.8 ± 17.1 (MPM) and 26.2 ± 12.4 (PAE).
• Main results:
  • Among the 19 PAE subjects, 16 had pleural plaques on chest x-ray and two had a radiological diagnosis of asbestosis.
  • In screening, 435 of 754 microRNAs were detectable. In MPM patients, 62 microRNAs were more than two-fold lower than in PAE subjects.
  • In validation, which included 22 MPM and 16 PAE subjects, 16 of the top 20 microRNAs were confirmed as significantly lower in MPM.
  • The combination of miR-103a-3p and miR-30e-3p distinguished MPM from PAE subjects with an AUC of 0.942 (95% CI 0.875 to 1.00), sensitivity 95.5% and specificity 80.0%.
  • In PAE subjects, miR-103a-3p and miR-30e-3p levels were not associated with years of asbestos exposure (p = 0.28 and p = 0.26).
  • All but three MPM patients had died by January 2016. MPM patients with miR-103a-3p or miR-30e-3p above the median had better survival, but this was not statistically significant (p = 0.07 and p = 0.18).
  • In adjusted Cox models of MPM patients, the hazard ratio for death with levels above the median was 0.37 (95% CI 0.13 to 1.13) for miR-103a-3p and 0.51 (95% CI 0.17 to 1.52) for miR-30e-3p.
• The authors' conclusion: The authors concluded that their findings suggest a microRNA signature in plasma extracellular vesicles able to discriminate MPM patients from subjects with past asbestos exposure. They called for larger, prospective studies to confirm it.
• Limitations the authors state:
  • Small number of subjects
  • No subjects with other chest diseases (such as lung cancer, pleural metastasis or benign pleural effusion) were included, which prevents firm conclusions
  • The small sample size prevents firm conclusions about better survival with higher levels of these microRNAs

Topics

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

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

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• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)
• Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies — L. Santarelli, S. Gaetani, et al. (2019)
• Small Extracellular Vesicle-Derived Circular RNA hsa_circ_0007386 as a Biomarker for the Diagnosis of Pleural Mesothelioma — S. Zhand, J. Liao, et al. (2024)

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