MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma

Our plain-English summary of MicroRNA-98 is a prognostic factor for asbestos-induced mesothelioma, by K. Kim, Y. Ko, H. Oh, et al (Journal of Toxicology and Environmental Health. Part a, 2020).

The study

• Authors: K. Kim, Y. Ko, H. Oh, M. Ha, J. Kang, E.J. Kwon, J.W. Kang, Y. Kim, H.J. Heo, G. Kim, J.W. Kim, Y.H. Kim
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2020;83(3):126-134
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.Abbreviations: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.

In plain English

This study re-analyzed existing genetic and clinical data rather than collecting new samples. In March 2019 the authors downloaded data from The Cancer Genome Atlas on 70 patients with malignant pleural mesothelioma: 56 recorded as asbestos-exposed and 14 as not exposed. They compared gene activity (messenger RNA) and small regulatory molecules called microRNAs between the two groups. No messenger RNA differed significantly. Twelve microRNAs were first selected. In a second dataset of 26 patients, 21 previously exposed to asbestos and 5 with unknown exposure, three of these did not differ markedly. The authors reported the remaining nine as lower in the exposed group of the main dataset. In survival analysis, only one, hsa-miR-98, was significantly linked to shorter survival in the asbestos-exposed group, with higher levels going with shorter survival. The authors called this surprising, given earlier reports that miR-98 suppresses tumors. They suggested that controlling asbestos-induced mesothelioma might require high levels of hsa-miR-98. They noted the small sample and that exposure was recorded only as yes or no, without fiber type or exposure period. The second dataset did not include miR-98.

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: Retrospective analysis of publicly available genomic and clinical data (The Cancer Genome Atlas), comparing asbestos-exposed and non-exposed patients, with a second public dataset (GEO GSE92636) used for validation
• Who was studied: 70 patients with malignant pleural mesothelioma from The Cancer Genome Atlas (56 asbestos-exposed, 14 non-exposed), data downloaded March 2019. The validation dataset had 26 patients: 21 asbestos-exposed and 5 with 'unknown' exposure.
• Exposure: Asbestos exposure recorded only as exposed or not exposed. No fiber type, exposure period or dose was analyzed.
• Main results:
  • None of the messenger RNAs differed significantly between the asbestos-exposed and non-exposed groups.
  • Of 12 microRNAs initially selected, three (hsa-let-7g, hsa-miR-126, hsa-181a-2) did not differ markedly by asbestos exposure in the validation dataset. In that dataset 21 of 26 patients had been exposed to asbestos and 5 had 'unknown' exposure.
  • Nine selected microRNAs were lower (down-regulated) in the asbestos-exposed group than in the non-exposed group.
  • In the asbestos-exposed group, only hsa-miR-98 was significantly associated with shorter survival. The other microRNAs showed no such effect. No hazard ratio or p-value is given in the text; the result is shown in Figure 2.
  • Higher hsa-miR-98 expression went with shorter survival, which the authors described as surprising.
  • Pathway analysis of the selected microRNAs identified five top pathways: fatty acid biosynthesis, proteoglycans in cancer, ECM-receptor interaction, Hippo signaling pathway and adherens junction.
  • In the main dataset, the exposed and non-exposed groups did not differ statistically in any recorded characteristic except laterality (which side of the chest was affected), p = 0.026.
• The authors' conclusion: The authors concluded that management of the aggressiveness and progression of asbestos-induced malignant pleural mesothelioma might require high levels of hsa-miR-98 because of its tumor-suppressive role. They said the study might help in understanding biological mechanisms of mesothelioma in asbestos-exposed patients or in studying targeted therapy.
• Limitations the authors state:
  • Only 70 patients were suitable for analysis. A larger sample might have given statistically stronger results.
  • Exposure was analyzed only as present or absent, not by fiber type or exposure period.
  • The database lacked chromosomal arm-level (3p, 5p) information on microRNAs, which limited interpretation of the pathway results.
  • In the validation dataset, information on previous asbestos exposure was limited and fewer microRNAs were available. Another independent dataset is needed.
  • Survival validation could be done only for three microRNAs present in the validation dataset; hsa-miR-98 was not among them.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Prognosis, Mineral Fiber, Kaplan-Meier Curve, Targeted Therapy, Discovery, Malignant Mesothelioma.

Related studies

• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)
• Prognostic and Therapeutic Implications of MicroRNA in Malignant Pleural Mesothelioma — A. Truini, S. Coco, et al. (2016)
• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma — T. Muraoka, J. Soh, et al. (2013)
• MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma — E. Sturchio, M.G. Berardinelli, et al. (2020)
• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)

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