Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma

Our plain-English summary of Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma, by V. Filetti, C. Loreto, L. Falzone, et al (Journal of Personalized Medicine, 2021).

The study

• Authors: V. Filetti, C. Loreto, L. Falzone, C. Lombardo, E. Cannizzaro, S. Castorina, C. Ledda, V. Rapisarda
• Journal: Journal of Personalized Medicine
• Published: 2021;11(11)
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Fluoro-edenite (FE) is an asbestiform fiber identified in Biancavilla (Sicily, Italy). Environmental exposure to FE has been associated with a higher incidence of malignant mesothelioma (MM). The present study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched with healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR (ddPCR) to evaluate differences in the expression levels of the selected miRNAs and their MM diagnostic potential. In addition, further computational analysis has been performed to establish the correlation of these miRNAs with the available online asbestos exposure data and clinic-pathological parameters to verify the potential role of these miRNAs as prognostic tools. ddPCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. Receiver operating characteristic (ROC) analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased overall survival (OS) of MM patients.

In plain English

This laboratory study measured three microRNAs (hsa-miR-323a-3p, hsa-miR-101-3p and hsa-miR-20b-5p) in stored tissue. It compared malignant mesothelioma tissue from 10 patients from Biancavilla, Sicily, whose disease the authors linked to fluoro-edenite, an asbestiform fiber, with non-cancerous pleura from 8 men living elsewhere who had pulmonary emphysema or pleurisy. All three microRNAs were significantly lower in the mesothelioma tissue. In this small group, miR-323a-3p and miR-20b-5p each separated cases from controls with 100% sensitivity and 100% specificity. miR-101-3p had 100% sensitivity and 40% specificity. A separate computer analysis of a public database of 87 mesothelioma samples found no significant difference in the three microRNAs between the 35 asbestos-exposed and 49 unexposed patients (3 were excluded for missing information), or across tumor stages. In that database, higher miR-101-3p was associated with longer survival. The authors described the data as preliminary and said the microRNAs should be evaluated further with more samples. They named the small number of samples and the lack of testing on an independent sample as limitations. They also said a group of fluoro-edenite-exposed people without tumors would be useful.

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 laboratory comparison of archived tissue from mesothelioma cases and non-cancer controls using droplet digital PCR, plus computer (in silico) analysis of a public mesothelioma database (TCGA-MESO) and gene-target prediction tools
• Who was studied: 10 malignant mesothelioma patients from Biancavilla, Sicily, Italy (6 men, 4 women; mean age 68.4 ± 13.9 years, range 50–93; 6 epithelioid, 3 biphasic, 1 sarcomatoid), from a University of Catania biobank. The 8 controls were all men (mean age 44 ± 25.5 years, range 15–76) who did not live in Biancavilla and had pulmonary emphysema (n = 3) or pleurisy (n = 5). The database contained 87 mesothelioma samples: 35 exposed to asbestos, 49 not exposed, and 3 excluded for lack of useful information. Collection dates are not given.
• Exposure: Environmental fluoro-edenite (an asbestiform fiber) in Biancavilla residents. No individual exposure measurements are reported. In the database analysis, patients were grouped as exposed or not exposed to asbestos.
• Main results:
  • All three microRNAs were significantly lower in the mesothelioma tissue than in the control tissue.
  • In the 10 cases versus 8 controls, hsa-miR-323a-3p and hsa-miR-20b-5p each had 100% sensitivity and 100% specificity (AUC = 1).
  • hsa-miR-101-3p had 100% sensitivity and 40% specificity (AUC = 0.8625). The AUCs of all three microRNAs were statistically significant (p less than 0.05).
  • In the database samples, levels of the three microRNAs did not change significantly between the 35 patients exposed to asbestos and the 49 not exposed. Three samples were excluded for lack of useful information.
  • In the database samples, levels of the three microRNAs did not change significantly across tumor stages.
  • In the database samples, high hsa-miR-101-3p expression was associated with longer overall survival, disease-specific survival and progression-free interval (p less than 0.0001).
  • In the database samples, hsa-miR-323a-3p and hsa-miR-20b-5p showed no significant results for survival.
  • A computer prediction tool indicated that the three microRNAs could interact with all 20 frequently mutated mesothelioma genes examined.
• The authors' conclusion: The authors called the data preliminary. They concluded that, with more samples, these microRNAs should be further evaluated as diagnostic tools and as predictors of prognosis.
• Limitations the authors state:
  • The number of samples available was low.
  • The sensitivity and specificity figures come from ROC curves in the same samples and have not been tested on an independent sample.
  • There was no group of people exposed to fluoro-edenite who did not have tumors.
  • The results for hsa-miR-323a-3p and hsa-miR-20b-5p were opposite to those of the authors' earlier computer and cell-culture analysis.

Topics

Medical terms in this study, explained in our Lexicon: Asbestiform, Malignant Mesothelioma, fluoro-edenite, Biancavilla, Environmental Exposure, Pleura, Asbestos Exposure, Overall Survival.

Related studies

• MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma — E. Sturchio, M.G. Berardinelli, et al. (2020)
• Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1 — C. Loreto, R. Caltabiano, et al. (2020)
• Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers — V. Filetti, C. Lombardo, et al. (2023)
• Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis — L. Micolucci, M.M. Akhtar, et al. (2016)
• Progress of research on microRNAs with diagnostic value in asbestos exposure: A call for method standardization — L. Micolucci, M.R. Rippo, et al. (2017)
• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)

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