Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos

Our plain-English summary of Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos, by G. Di Mauro, F. Frontini, E. Torreggiani, et al (Scientific Reports, 2023).

The study

• Authors: G. Di Mauro, F. Frontini, E. Torreggiani, M.R. Iaquinta, A. Caselli, C. Mazziotta, V. Esposito, E. Mazzoni, R. Libener, F. Grosso, A. Maconi, F. Martini, I. Bononi, M. Tognon
• Journal: Scientific Reports
• Published: 2023;13(1):6501
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.

© 2023. The Author(s).

In plain English

This Italian laboratory study measured a small RNA molecule, microRNA-197-3p, in stored blood serum from 75 patients with malignant pleural mesothelioma, 75 workers previously exposed to asbestos, and 75 healthy subjects. The authors used two methods, droplet digital PCR (ddPCR) and real-time quantitative PCR (RT-qPCR). With ddPCR, mean levels were 981.7 copies/µl in the patients, 525.01 in the exposed workers and 1,085 in the healthy subjects. The patients differed significantly from the workers, but not from the healthy subjects. With RT-qPCR, levels were also higher in patients than in workers (603.7 versus 336.1), but no difference between groups was statistically significant. The test separated patients from workers only modestly, which the authors called at the limit of acceptability for a marker. The study found no statistically significant difference in microRNA levels between tumor subtypes, and no statistically significant link between microRNA levels and survival at 18 months. Survival was linked to tumor subtype and to pleurectomy. The authors concluded the test could be added as a minimally invasive screening test to follow up exposed workers.

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: Laboratory biomarker study comparing serum microRNA-197-3p levels across three groups (mesothelioma patients, asbestos-exposed workers, healthy subjects) using two PCR techniques, with survival analysis in the patient group
• Who was studied: 225 serum samples from Italy: 75 malignant pleural mesothelioma patients (Mesothelioma BioBank, City Hospital of Alessandria), 75 workers ex-exposed to asbestos (Occupational Medicine Unit, University of Ferrara), and 75 healthy subjects (discarded laboratory samples, University Hospital of Ferrara). Mean ages were about 66 to 70 years. Collection dates are not given.
• Exposure: Past asbestos exposure in the worker group, with exposure data taken from the authors' previous study; no fiber types are named. In the mesothelioma group, asbestos exposure was recorded as professional documented (17), professional possible (5), domestic/environmental (14), none (2), or not available (37).
• Main results:
  • By ddPCR, mean miR-197-3p was 981.7 plus or minus 123.7 copies/µl in mesothelioma patients, 525.01 plus or minus 62.13 in exposed workers, and 1,085 plus or minus 141.3 in healthy subjects (mean plus or minus SEM)
  • By ddPCR, mesothelioma patients differed significantly from exposed workers (P = 0.0036), and workers differed from healthy subjects (P = 0.0001), but patients did not differ from healthy subjects
  • ddPCR discrimination between mesothelioma patients and exposed workers: area under the curve 0.65 (P = 0.001; 95% confidence interval 0.563 to 0.739). For patients versus healthy subjects it was 0.55, not significant.
  • By RT-qPCR, means were 603.7 plus or minus 82.51 copies/µl in mesothelioma patients, 336.1 plus or minus 43.39 in exposed workers, and 557.8 plus or minus 101.1 in healthy subjects. No difference among the three groups or between any pair was statistically significant.
  • RT-qPCR discrimination between mesothelioma patients and exposed workers: area under the curve 0.62 (P = 0.014; 95% confidence interval 0.525 to 0.708). For patients versus healthy subjects the result was not significant.
  • With both techniques, miR-197-3p levels showed no statistically significant difference among the epithelioid, sarcomatoid and biphasic subtypes
  • In the 75 mesothelioma patients, the authors found no statistically significant association between miR-197-3p level and overall survival at 18 months (P > 0.05). The authors describe this as OS not being influenced by miR-197-3p.
  • Histologic subtype significantly influenced overall survival (log-rank P = 0.0056): 40.7% for epithelioid, 28.6% for biphasic and 15% for sarcomatoid
  • Overall survival was 62.5% in patients who had pleurectomy (8 of 75 patients) versus 25.4% in unoperated patients (log-rank P = 0.0394)
  • No correlation was found between overall survival and asbestos exposure or smoking status in the mesothelioma patients (P > 0.05 for each)
• The authors' conclusion: The authors concluded that circulating miR-197-3p could be added as a minimally invasive screening test to follow up workers ex-exposed to asbestos, whom they describe as at high risk of developing mesothelioma
• Limitations the authors state:
  • The authors stated that the areas under the curve (0.62 and 0.65) were at the limit of acceptability for a marker, compared with values above 0.70 to 0.80 reported in the literature
  • Clinical, occupational and non-occupational information could not be obtained for all mesothelioma patients. For example, asbestos exposure was unavailable for 37 of 75 patients and smoking status for 40 of 75.
  • The two techniques disagreed on statistical significance, which the authors attribute to RT-qPCR being less accurate than ddPCR

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, Overall Survival, Histological Subtype, Biomarker, Chest X-Ray, Spirometry.

Related studies

• Circulating microRNA-197-3p as a potential biomarker for asbestos exposure — F. Frontini, I. Bononi, et al. (2021)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study — D.G. Weber, A. Brik, et al. (2019)
• The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma — T. Muraoka, J. Soh, et al. (2013)
• Droplet digital PCR as a novel system for the detection of microRNA‑34b/c methylation in circulating DNA in malignant pleural mesothelioma — H. Sato, J. Soh, et al. (2019)
• Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein — E. Mazzoni, I. Bononi, et al. (2022)

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