Prognostic and Therapeutic Implications of MicroRNA in Malignant Pleural Mesothelioma

Our plain-English summary of Prognostic and Therapeutic Implications of MicroRNA in Malignant Pleural Mesothelioma, by A. Truini, S. Coco, C. Genova, et al (MicroRNA, 2016).

The study

• Authors: A. Truini, S. Coco, C. Genova, M. Mora, M.G. Dal Bello, I. Vanni, A. Alama, E. Rijavec, G. Barletta, F. Biello, C. Maggioni, F. Grossi
• Journal: MicroRNA
• Published: 2016;5(1):12-18
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant Pleural Mesothelioma (MPM) is an aggressive disease characterized by a dismal prognosis, mainly due to late diagnosis. To date, there are very few treatment options available and the refractoriness to the majority of therapeutic strategies, leading to consider MPM a relevant problem in public health. Therefore, the identification of novel prognostic markers and alternative therapeutic strategies remain a top priority. Several efforts have been made in this direction and to date a number of studies have investigated the role of microRNA as biomarkers in MPM, identifying the potential prognostic role of miR-29c* and miR-31. Very recently, the first microRNA signature able to discriminate poor or and good prognosis of MPM patients underwent surgery has been published. Very interestingly, several microRNA such as miR-1, miR-16, and miR-34b/c have been identified as potential therapeutic agents. Indeed, the forced expression of these microRNA resulted in anti-tumor effects both in vitro and in vivo. Besides, the introduction of microRNA mimic, some agents such as EphrinA1 and Onconase, seemed to exert anti-tumor effects through specific microRNA. Moreover, microRNA have also been reported to play a role in chemoresistance enhancing the sensitivity to specific drug such as pemetrexed. In this review the most relevant and updated data about the role of microRNA as prognostic markers and therapeutic agents in MPM will be presented, opening new avenues towards improved management of this aggressive disease.

In plain English

This is a review article, not a new study. The authors, from a lung cancer unit and a pathology department in Genova, Italy, summarized published research on microRNA (small non-protein-coding RNA that regulate gene expression) in malignant pleural mesothelioma (MPM). They describe MPM as associated with professional or environmental exposure to asbestos. They did not describe how the studies were selected. Among the studies reviewed, Pass and colleagues reported that among surgically resected patients in the epithelial group, higher miR-29c* levels went with longer survival (21.6 versus 9.1 months). Kirschner and colleagues reported a six-microRNA signature, the "miR-Score", that predicted survival in patients who had surgery. Other reviewed studies, mostly in laboratory cell lines and mice, reported that restoring miR-34b/c, miR-1, miR-16 or miR-193a-3p slowed tumor growth. In MPM cell-line experiments, some microRNA increased sensitivity to radiation or to drugs such as pemetrexed. The authors noted that few studies exist, results sometimes conflict, and methods need standardization. No microRNA has reached clinical use, partly for lack of an efficient delivery technique. The authors concluded that targeting microRNA may represent a potential therapeutic strategy.

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 microRNA as prognostic markers and therapeutic agents in malignant pleural mesothelioma; no study selection method is described
• Who was studied: No population of its own. The reviewed studies used MPM tumor samples, MPM cell lines, normal mesothelial cells and mouse models.
• Exposure: The review does not study asbestos exposure. Asbestos is mentioned only in the background as associated with MPM. The subject is microRNA levels and experimental microRNA treatments.
• Main results:
  • Reviewed study by Pass and colleagues (129 fresh frozen samples from resected MPM patients): in the epithelial cohort, high miR-29c* expression was associated with an overall survival of 21.6 months, versus 9.1 months with low expression.
  • Reviewed study by Matsumoto and colleagues (25 MPM samples): patients with upregulated miR-31 had shorter overall survival than those with downregulated or normal levels (5.3 vs 27.3 and 30.1 months).
  • Reviewed study by Kirschner and colleagues: a 6-microRNA signature (miR-Score) in patients who had extrapleural pneumonectomy gave an AUC of 0.867. In a validation cohort of patients who had palliative surgery, accuracy was 71.9%, with survival of 15.4 vs 6.5 months for good vs poor prognosis.
  • Reviewed study by Kubo and colleagues: aberrant methylation of miR-34b/c was found in 85.1% of clinical samples.
  • Reviewed mouse study (Ueno and colleagues): adenovirus-delivered miR-34b/c produced statistically significant inhibition of growth of transplanted human MPM cells, starting from day 6.
  • Reviewed study by Reid and colleagues: intravenous miR-16 mimic inhibited tumor growth in nude mice. In cell lines, miR-16 increased sensitivity to gemcitabine and pemetrexed.
  • Reviewed study by Maki and colleagues: in 2 MPM cell lines, miR-34b/c increased sensitivity to radiation compared with untransfected cell lines.
  • Reviewed study by Williams and colleagues: miR-193a-3p inhibited growth of MPM cell lines, but neither miR-192 nor miR-193a-3p increased drug sensitivity.
  • Reviewed study by Yamamoto and colleagues: in MPM cell lines, re-expression of miR-379 and miR-411 increased sensitivity to pemetrexed and vorinostat.
• The authors' conclusion: The authors concluded that the reviewed studies point to a prognostic role and a tumor-suppressor function of specific microRNA, and that targeting their expression may be a potential therapeutic strategy. They called for carriers that improve microRNA delivery.
• Limitations the authors state:
  • Relatively few studies have examined microRNA in MPM, and results differ between studies.
  • The field lacks methodological standardization, and results depend on the type of sample analyzed (tissue, cell lines, serum, plasma).
  • No microRNA has entered clinical use. Efficient delivery techniques are lacking.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Biomarker, Pemetrexed (Alimta).

Related studies

• Role of microRNAs in malignant mesothelioma — A. Truini, S. Coco, et al. (2014)
• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)
• MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma — K. Kim, Y. Ko, et al. (2020)
• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma — E. Sturchio, M.G. Berardinelli, et al. (2020)
• A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma — H. Benjamin, D. Lebanony, et al. (2010)

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