Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Our plain-English summary of Circulating microRNA-197-3p as a potential biomarker for asbestos exposure, by F. Frontini, I. Bononi, E. Torreggiani, et al (Scientific Reports, 2021).

The study

• Authors: F. Frontini, I. Bononi, E. Torreggiani, G. Di Mauro, E. Mazzoni, M. Stendardo, P. Boschetto, R. Libener, R. Guaschino, F. Grosso, G. Guerra, F. Martini, M. Tognon
• Journal: Scientific Reports
• Published: 2021;11(1):23955
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

© 2021. The Author(s).

In plain English

This Italian laboratory study measured microRNA-197-3p, a short strand of RNA, in serum from 75 workers formerly exposed to asbestos and from 62 healthy subjects of similar age. Workers with malignant pleural mesothelioma were excluded. The workers were grouped by cumulative asbestos exposure, in fibers per cubic centimeter of air; fiber types were not named. With two laboratory methods, average levels were lower in the former workers than in healthy subjects. By RT-qPCR they were 336.0 versus 870.1 copies per microliter of cDNA, a laboratory copy of the extracted RNA, not of serum (reported as 2.6 times lower). By ddPCR they were 525.0 versus 1316 (2.5 times lower). Among the workers, ddPCR levels in the highest exposure group (above 55 fibers/cc) averaged 326.2. That was significantly lower than in the two lower groups (667.8 and 712.3). By RT-qPCR the differences between exposure groups were not statistically significant. No statistically significant correlation was found with years of exposure, time since exposure, smoking, or asbestos-related conditions. The authors concluded that miR-197-3p is a new biomarker for asbestos exposure and cumulative exposure levels.

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 comparison of serum microRNA levels between former asbestos-exposed workers and healthy subjects, using two PCR methods (RT-qPCR and ddPCR)
• Who was studied: 75 workers formerly exposed to asbestos (WEA), volunteers from two post-occupational medical surveillance centers in Italy (Dolo and the University of Ferrara), excluded if they had malignant pleural mesothelioma. Also 62 healthy subjects (HS) attending the University Hospital of Ferrara laboratory for a routine check-up. Mean ages were 66.3 years (SD 6.6) for WEA and 65.3 years (SD 17.0) for HS.
• Exposure: Past occupational asbestos exposure; fiber types not specified. Workers were grouped by cumulative asbestos exposure: range 1, 0 to 8 fibers/cc; range 2, 8 (8.1 in Table 1) to 55 fibers/cc; range 3, above 55 fibers/cc. Exposure data were available for 64 of 75 workers.
• Main results:
  • By RT-qPCR, the mean miR-197-3p level was 336.0 copies/µl in WEA versus 870.1 copies/µl of cDNA in HS (t-test p = 0.0001), reported as 2.6 times lower in WEA. All levels in the article are expressed as copies per microliter of analyzed cDNA.
  • ROC analysis for RT-qPCR in WEA versus HS gave an AUC of 0.727 (95% confidence interval 0.641 to 0.813)
  • By ddPCR, the mean level was 525.0 copies/µl in WEA versus 1316 copies/µl of cDNA in HS (t-test p less than 0.0001), reported as 2.5 times lower in WEA
  • ROC analysis for ddPCR in WEA versus HS gave an AUC of 0.755 (95% confidence interval 0.675 to 0.835)
  • Values from the two methods were correlated (R-square 0.900)
  • Within WEA, the RT-qPCR means by cumulative exposure range were 352.7 (range 1), 465.9 (range 2) and 245.9 (range 3) copies/µl. These differences were not statistically significant.
  • Within WEA, the ddPCR means were 667.8 (range 1), 712.3 (range 2) and 326.2 (range 3) copies/µl. Range 3 differed significantly from range 1 (p = 0.0297; 2.0-fold) and from range 2 (p = 0.0239; 2.1-fold).
  • Spearman correlation with cumulative exposure in WEA was -0.389 by ddPCR (statistically significant) and -0.197 by RT-qPCR (not marked significant)
  • No statistically significant correlation was found with exposure duration, years since last exposure, tobacco, asbestosis or other asbestos-related pathologies, other diseases, or therapies
• The authors' conclusion: The authors concluded that miR-197-3p is a new biomarker for asbestos exposure and cumulative asbestos levels in former exposed workers. They inferred that inhaled fibers affect its levels and said further investigations are needed.

Topics

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

Related studies

• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos — G. Di Mauro, F. Frontini, et al. (2023)
• 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)
• Increased circulating miR-625-3p: a potential biomarker for patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2012)
• Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease — T. Cavalleri, L. Angelici, et al. (2017)
• The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma — T. Muraoka, J. Soh, et al. (2013)

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