MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets

Our plain-English summary of MicroRNAs in mesothelioma: from tumour suppressors and biomarkers to therapeutic targets, by G. Reid (Journal of Thoracic Disease, 2015).

The study

• Author: G. Reid
• Journal: Journal of Thoracic Disease
• Published: 2015;7(6):1031-40
• Type of article: Review
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma remains a difficult proposition in the clinic, with few accurate molecular markers available to guide diagnosis and patient management, and a dearth of effective treatments. Recent evidence implicates microRNAs-short non-coding RNAs involved in post-transcriptional regulation of gene expression-in mesothelioma biology. Emerging evidence suggests that exploring aberrant microRNA expression will not only improve our understanding of the disease, but will also lead to the identification of new molecular biomarkers and therapeutic targets.

In plain English

This article was a review, not a new study. Written by an author from the Asbestos Diseases Research Institute in Sydney, it surveyed published research on microRNAs in malignant pleural mesothelioma. MicroRNAs are short pieces of genetic material that help control which proteins a cell makes. The article describes this mesothelioma as an asbestos-induced cancer. The author counted around 50 studies and described those on tumour biology, biomarkers and treatment. In the reviewed laboratory studies, many microRNAs were reduced in mesothelioma, and restoring them slowed mesothelioma cells grown in the laboratory. Among the biomarker studies, a three-microRNA signature identified blinded samples (14 mesothelioma, 49 adenocarcinomas) with 95% accuracy. That assessment became the basis of a diagnostic test offered by the company Rosetta Genomics. In another, miR-126 was significantly lower in serum from mesothelioma patients than from asbestos-exposed or healthy controls. In a mouse study, delivering miR-16 controlled tumour growth, and a first human trial was underway. The author concluded that there is considerable evidence implicating microRNAs in mesothelioma growth, invasion and drug resistance. The author added that the biomarker findings need independent validation and standardized methods.

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: Narrative review of published studies on microRNAs in malignant pleural mesothelioma (no new data; no search method described)
• Who was studied: Published studies of microRNA expression in malignant pleural mesothelioma (MPM): cell lines, tumour samples, blood samples and mouse experiments. The author reported around 50 such studies. No search dates were given.
• Exposure: The review studied microRNA levels, not asbestos exposure. It describes malignant pleural mesothelioma as asbestos-induced but names no fiber types. Some reviewed blood studies used asbestos-exposed people as controls.
• Main results:
  • Across the reviewed studies, microRNA expression was generally reduced in malignant pleural mesothelioma.
  • Most of the reduced microRNAs showed tumour-suppressor activity when restored in mesothelioma cells grown in the laboratory.
  • In a reviewed study by Rosetta Genomics (reference 42), a signature of three microRNAs (miR-192, miR-200c and miR-193a-3p) identified blinded samples from an independent set (14 mesothelioma, 49 adenocarcinomas) with 95% accuracy. The article says this assessment is the basis of the company's diagnostic test. It does not report the accuracy of the marketed test in use.
  • In a reviewed study (reference 46) of 44 mesothelioma patients, 196 asbestos-exposed controls and 50 healthy controls, miR-126 was significantly lower in serum from the mesothelioma patients than from either control group. The author described its power to tell the groups apart as moderate.
  • In a reviewed whole-blood study (reference 45), lower miR-103 levels separated mesothelioma patients from healthy controls (AUC 0.871) better than from asbestos-exposed controls (AUC 0.757). The author noted the numbers were small (23 patients, 17 controls).
  • In a reviewed prognosis study (reference 44), a six-microRNA signature in surgical specimens showed a statistically significant survival difference of 22.9 months between score-positive and score-negative groups. In a validation group of patients who had pleurectomy/decortication, the survival difference was 8.9 months.
  • In a reviewed mouse study (reference 25, whose authors include this review's author), a miR-16 mimic delivered by EGFR-targeted bacterial minicells controlled the growth of mesothelioma xenografts. A phase I study in patients with mesothelioma and non-small cell lung cancer was underway in Sydney.
• The authors' conclusion: The author concluded that there is considerable evidence implicating microRNAs in mesothelioma growth, invasion and drug resistance. The author added that microRNAs in patients' tumours and blood have yielded several biomarker candidates.
• Limitations the authors state:
  • The author stated that the reviewed blood biomarker findings need independent validation, preferably in prospective studies, and that methods need to be standardized.
  • The author noted that measuring microRNAs in plasma and serum is open to several sources of error, including hemolysis (breakdown of red blood cells).
  • The author noted that most studies of what restored microRNAs do were limited to cells grown in the laboratory. Only four studies showed an effect in living animals.

Topics

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

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