MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review

Our plain-English summary of MicroRNAs for the Diagnosis and Management of Malignant Pleural Mesothelioma: A Literature Review, by G. Lo Russo, A. Tessari, M. Capece, et al (Frontiers in Oncology, 2018).

The study

• Authors: G. Lo Russo, A. Tessari, M. Capece, G. Galli, F. de Braud, M.C. Garassino, D. Palmieri
• Journal: Frontiers in Oncology
• Published: 2018;8:650
• Type of article: Review
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis per se is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.

In plain English

This article was a literature review, not a new study. The authors collected and discussed published research on microRNAs in malignant pleural mesothelioma. MicroRNAs are small molecules that help control how genes are used. Malignant pleural mesothelioma is a cancer that starts in the pleura, the lining around the lungs, and the authors name occupational asbestos exposure as its most important cause. The reviewed work included laboratory studies in cell lines and mice, and studies that measured microRNAs in tumor tissue, pleural fluid and blood. Some of these compared mesothelioma patients with asbestos-exposed people who did not have cancer. The authors reported that several microRNAs had been linked to diagnosis or prognosis in more than one study. They also reported that only one human trial of a microRNA-based treatment had published results: an early-phase study in which 26 patients were treated. The authors concluded that microRNAs have great potential for diagnosis and treatment. They also stated that the reviewed studies used very different methods, samples and control groups, which limits how well the results can be reproduced, and they called for coordinated international research.

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: Literature review (narrative review of published studies)
• Who was studied: No new patients were studied. The review covered published studies on microRNAs in malignant pleural mesothelioma (MPM). These were laboratory studies in cell lines and mouse models, and studies of tumor tissue, pleural effusion and blood samples from patients and comparison groups. It also covered one phase I clinical trial.
• Exposure: Not an exposure study; the subject was microRNAs in MPM. The authors name occupational asbestos exposure as the most important cause of MPM. Some of the reviewed studies used asbestos-exposed people without cancer as a comparison group.
• Main results:
  • The authors reported that specific microRNAs had been reported several times by different research groups: let-7, miR-15 and miR-16, miR-21, miR-34a and the miR-200 family.
  • According to the authors, the role of some microRNAs as diagnostic or prognostic markers in MPM had been confirmed in more than one study. In some cases this evidence was becoming more solid: miR-16, miR-103, miR-126, miR-145 and miR-200c.
  • The review describes a reviewed study by Weber et al. of 52 asbestos-exposed and 43 MPM male patients. For telling these two groups apart, sensitivity was 89% for miR-103a-3p, 74% for mesothelin and 95% for the two combined. Specificity was 63%, 85% and 81%, respectively.
  • Treatments that restore microRNAs in MPM had been tested in cell lines and mouse models.
  • Only one clinical trial in humans (NCT02369198) had published results. In this phase I study, TargomiRs (minicells loaded with a miR-16 mimic) were given to patients whose MPM had progressed after chemotherapy. Twenty-seven patients were enrolled and 26 were treated. Median overall survival was 200 days (95% CI 94-358). As best response, 5% had partial response, 68% stable disease and 27% progressive disease.
  • In that trial, the most common adverse events were transient lymphopenia (96%), hypophosphataemia (65%) and increased transaminase levels (23%). Cardiac events (18%) occurred in five cases.
• The authors' conclusion: The authors concluded that measuring and analyzing microRNAs in MPM tissues and body fluids has great potential for diagnosis and therapy. They added that microRNA-based therapies still lack appropriate clinical validation, and they urged coordinated collaboration among international research groups.
• Limitations the authors state:
  • The reviewed studies varied widely in how microRNAs were measured and in the types of samples and controls used.
  • In some reviewed studies, data were poorly defined, important information was missing, or the statistical analysis was not adequate.
  • Some studies used healthy people as controls, while others included people with non-cancer lung disease or asbestos-exposed people without cancer in the same control group. The authors said this could lead to missing or misidentifying microRNAs.
  • Results had limited reproducibility, which the authors said strongly affects the possibility of combining published studies in a meta-analysis.
  • MicroRNA-based therapies still lack appropriate clinical validation. Their effects on normal cells are unclear, and cancer-specific delivery systems are still needed.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Latency, Prognosis, Chemotherapy, Biomarker, Discovery, Carcinogenesis.

Related studies

• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Young investigator challenge: MicroRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology — R. Cappellesso, L. Nicolè, et al. (2016)
• The role of microRNAs in the diagnosis and treatment of malignant pleural mesothelioma--a short review — K.W. Sheff, M.A. Hoda, et al. (2012)
• Diagnosis and initial management of nonmalignant diseases related to asbestos — American Thoracic Society (2004)
• Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma — D.H. Sterman, S.M. Albelda (2005)

Browse more research in Frontiers in Oncology, or return to medical research.