MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion

Our plain-English summary of MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion, by G. Ak, S.C. Tomaszek, F. Kosari, et al (BioMed Research International, 2015).

The study

• Authors: G. Ak, S.C. Tomaszek, F. Kosari, M. Metintas, J.R. Jett, S. Metintas, H. Yildirim, E. Dundar, J. Dong, M.C. Aubry, D.A. Wigle, C.F. Thomas
• Journal: BioMed Research International
• Published: 2015;2015:635748
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion.

Methods: Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols.

Results: We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway.

Conclusions: Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma.

In plain English

This laboratory study compared frozen pleural tissue from 18 patients with malignant pleural mesothelioma and 6 patients with benign asbestos-related pleural effusion. All patients were diagnosed and followed at Eskisehir Osmangazi University Hospital in Turkey. A benign diagnosis required, among other things, a three-year observation period to exclude cancer. The authors measured microRNAs (small molecules that regulate genes) and gene activity (mRNA) in the tissue. Eleven microRNAs were significantly higher in mesothelioma tissue than in benign tissue. Four of them separated the two groups well: hsa-miR-484, hsa-miR-320, hsa-let-7a and hsa-miR-125a-5p. At a chosen cut-off, hsa-miR-484 had 100% sensitivity and specificity in these samples. No significant microRNA differences were found between mesothelioma subtypes or between early and late stages. The gene MET was the most overexpressed gene, more than 15-fold higher in mesothelioma than in benign tissue. A combined analysis pointed to eight pathways, two of them related to Notch signaling. The authors concluded that specific microRNAs may have diagnostic value in telling the two conditions apart. They said the results need validation in a larger group of patients.

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: Laboratory study comparing microRNA and mRNA expression in pleural tissue from mesothelioma patients and benign asbestos-related pleural effusion patients
• Who was studied: 18 patients with malignant pleural mesothelioma and 6 patients with benign asbestos-related pleural effusion, diagnosed and followed at Eskisehir Osmangazi University Hospital, Turkey. Tissue was analyzed at Mayo Clinic. Study dates are not stated.
• Exposure: Asbestos exposure history; no fiber types are named. Mean asbestos exposure time was 33.1 years (standard deviation 19.6, range 0 to 81) in the mesothelioma group and 28.2 years (standard deviation 11.3, range 20 to 49) in the benign effusion group.
• Main results:
  • Eleven microRNAs were significantly higher in mesothelioma tissue than in benign asbestos-related pleural effusion tissue. Fold changes ranged from 2.39 (hsa-miR-92a) to 13.93 (hsa-let-7a).
  • Four microRNAs had an area under the curve of 0.90 or more for telling mesothelioma from benign effusion. hsa-miR-484, at a cut-off of 8.15 or less, had 100% sensitivity and specificity.
  • The other three microRNAs had the following sensitivity and specificity: hsa-miR-320, 78% and 100%; hsa-let-7a, 94% and 83%; hsa-miR-125a-5p, 89% and 100%.
  • Within the mesothelioma samples, no significant microRNA differences were seen between epithelial, sarcomatous and mixed histology, or between early stage (I-II) and late stage (III-IV) disease.
  • MET was the most highly overexpressed gene in mesothelioma compared with benign effusion, at over 15-fold (15.56 in Table 5). It was also a target of microRNAs that were lower in mesothelioma.
  • The combined microRNA and mRNA analysis identified eight significant pathways, two of them related to Notch signaling.
• The authors' conclusion: The authors concluded that specific microRNAs may have diagnostic value in distinguishing mesothelioma from benign asbestos-related pleural effusion. They believed this would help asbestos-exposed patients with nonspecific pleuritis/fibrosis on biopsy, especially those from high-incidence regions. They also concluded that the genes and pathways they identified may have promise as treatment targets.
• Limitations the authors state:
  • The results need to be validated in a larger group of patients.
  • The authors attributed the lack of microRNA differences between histologic subtypes likely to most samples being epithelial.
  • The authors had no data on the SV40 virus status of their patients.

Topics

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

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

Related studies

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• Expression Profiles of Cytokine mRNAs in the Pleural Fluid Reveal Differences Among Tuberculosis, Malignancies, and Pneumonia-Exudative Pleural Effusions — D.L. Espósito, V.R. Bollela, et al. (2015)
• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)
• Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis of patients with pleural effusions: a randomized, controlled trial — M. Metintas, G. Ak, et al. (2010)
• Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets — E.G. Ramírez-Salazar, L.C. Salinas-Silva, et al. (2014)
• MicroRNAs dysregulation in human malignant pleural mesothelioma — V. Balatti, S. Maniero, et al. (2011)

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