Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers

Our plain-English summary of Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers, by I. Bononi, M. Comar, A. Puozzo, et al (Oncotarget, 2016).

The study

• Authors: I. Bononi, M. Comar, A. Puozzo, M. Stendardo, P. Boschetto, S. Orecchia, R. Libener, R. Guaschino, S. Pietrobon, M. Ferracin, M. Negrini, F. Martini, M. Bovenzi, M. Tognon
• Journal: Oncotarget
• Published: 2016;7(50):82700-82711
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarkers.

In plain English

This Italian laboratory study compared microRNAs, which are small RNA molecules, in blood serum from three groups: patients with malignant pleural mesothelioma (MPM), workers formerly exposed to asbestos fibers, and healthy subjects. The article does not name fiber types or exposure levels. A microarray screen of 1,201 microRNAs in 30 sera (10 per group) detected 145 microRNAs in healthy subjects, 119 in MPM patients and 42 in exposed workers. A second method, RT-qPCR, was used on 49 sera (20 MPM, 15 exposed workers, 14 healthy), with miR-3665 as a stable reference. By this method, miR-197-3p was higher in MPM patients than in healthy subjects (fold change 1.8, p = 0.0392) and than in exposed workers (2.5, p = 0.0194). miR-1281 was higher than in healthy subjects both in MPM patients (2.5, p = 0.0121) and in exposed workers (3.5). miR-32-3p appeared in 6 of 20 MPM sera and in none from the other groups. The authors proposed the three microRNAs as potential new MPM biomarkers. They speculated that the markers might help assess mesothelioma risk in exposed workers, and said the miR-197 finding needed confirmation.

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 circulating microRNAs in stored serum samples from three groups (mesothelioma patients, asbestos-exposed workers, healthy subjects). It used microarray screening, followed by RT-qPCR validation.
• Who was studied: Serum from patients with malignant pleural mesothelioma (MPM), workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS), collected in Ferrara and Alessandria, Italy. The microarray used 30 samples (10 per group, median age 64). RT-qPCR used 49 samples (20 MPM, 15 WEA, 14 HS, median age 65). No collection dates are given.
• Exposure: Past exposure to asbestos fibers. Fiber types, jobs, products and doses are not specified.
• Main results:
  • Of 1,201 microRNAs tested by microarray, 145 were detected in healthy subjects, 119 in MPM patients and 42 in exposed workers.
  • The authors reported p=0.053 for healthy subjects vs MPM, p<0.0001 for healthy subjects vs exposed workers, and p<0.0001 for MPM vs exposed workers. They called all three differences statistically significant, although their stated cutoff was p<0.05.
  • 52 microRNAs were detected only in MPM samples. None of the 42 microRNAs found in exposed workers was unique to that group.
  • In the microarray comparison across the three groups, 37 microRNAs were found significantly dysregulated (ANOVA).
  • miR-3665 was chosen as the stable reference microRNA for measuring the others.
  • By RT-qPCR, miR-197-3p was up-regulated in MPM patients compared with healthy subjects (fold change 1.8, p=0.0392) and with exposed workers (fold change 2.5, p=0.0194).
  • By RT-qPCR, miR-1281 was up-regulated in MPM patients compared with healthy subjects (fold change 2.5, p=0.0121).
  • By RT-qPCR, miR-1281 was up-regulated in exposed workers compared with healthy subjects (fold change 3.5). The p-value is printed in a garbled form.
  • By RT-qPCR, miR-32-3p was detected in 6 of 20 (30%) MPM sera and in none of the exposed-worker or healthy-subject sera.
• The authors' conclusion: The authors proposed up-regulated miR-197-3p, miR-1281 and miR-32-3p as new biomarkers for MPM and as potential treatment targets. They speculated that these markers could be used in asbestos-exposed workers to assess or predict mesothelioma risk over time.
• Limitations the authors state:
  • miR-32-3p was found in too few samples (12%) to calculate a fold difference and p-value.
  • The authors indicated that the miR-197 finding needs confirmation by other studies.

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, Biomarker, Occupational Disease, Latency.

Related studies

• Circulating microRNA-197-3p as a potential biomarker for asbestos exposure — F. Frontini, I. Bononi, et al. (2021)
• 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)
• miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer — K.M. Foss, C. Sima, et al. (2011)
• MicroRNAs dysregulation in human malignant pleural mesothelioma — V. Balatti, S. Maniero, et al. (2011)

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