Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers

Our plain-English summary of Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers, by C. Ledda, C. Loreto, C. Lombardo, et al (Translational Oncology, 2024).

The study

• Authors: C. Ledda, C. Loreto, C. Lombardo, V. Cardile, V. Rapisarda
• Journal: Translational Oncology
• Published: 2024;40:101872
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

Copyright © 2023. Published by Elsevier Inc.

In plain English

This nested case-control study compared 125 construction workers from Biancavilla, Sicily, Italy, with 125 construction workers who had worked at least 40 km away. In Biancavilla, stone quarried locally and used in building contains Fluoro-edenite (FE), an asbestos-like fiber. All participants had at least ten years in construction and no previous respiratory disorders. Their blood was tested for inflammation markers, for soluble mesothelin-related protein (SMRP), and for methylation of the mesothelin gene. Age, body mass index, smoking (6 % in each group) and years worked were similar between the groups. Exposed workers had significantly higher IL-1β, TNFα and SMRP levels. IL-6 and IL-8 did not differ significantly. The mesothelin gene was unmethylated in 57 of 125 exposed workers (46 %) compared with 112 of 125 non-exposed workers (90 %). It was fully methylated in 55 exposed workers (44 %) compared with 5 non-exposed workers (4 %). The authors said these changes suggest potential inflammatory responses and cellular changes due to occupational exposure. They noted that the study covered one region and only construction workers, and that unmeasured factors such as lifestyle habits or genetic predispositions may have influenced the results.

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: nested case-control study (exposed and control workers selected from a larger cohort the authors have monitored)
• Who was studied: 125 construction workers from Biancavilla (Sicily, Italy) and 125 control construction workers who had worked at least 40 km away from Biancavilla. All had at least ten years in construction and no previous respiratory disorders. Controls had no work history in Biancavilla and no historical asbestos exposure.
• Exposure: Fluoro-edenite (FE), a naturally occurring asbestiform fiber in material quarried near Biancavilla and used for about 50 years in local construction. Exposure was defined by construction work in Biancavilla; no individual exposure measurements are reported.
• Main results:
  • The groups were comparable in age, BMI, smoking and years worked. Smoking was 8 (6 %) in each group, and none of these differences was statistically significant.
  • IL-1β was higher in exposed workers (34.128 ± 5.977) than in non-exposed workers (22.175 ± 2.042), p less than 0.001.
  • TNFα was higher in exposed workers (30.724 ± 3.426) than in non-exposed workers (10.083 ± 1.710), p less than 0.001.
  • IL-6 and IL-8 did not differ significantly between groups.
  • SMRP was significantly higher in exposed workers (0.679 ± 0.406) than in non-exposed workers (0.372 ± 0.227), p less than 0.001.
  • The mesothelin gene was unmethylated in 57 (46 %) exposed workers compared with 112 (90 %) non-exposed workers.
  • The mesothelin gene was fully methylated in 55 (44 %) exposed workers compared with 5 (4 %) non-exposed workers, p less than 0.001.
  • In Pearson correlation analysis, IL-1β correlated positively with TNFα, and SMRP correlated positively with both IL-1β and TNFα (p less than 0.001). IL-8 correlated negatively with IL-1β, IL-6 and TNFα.
• The authors' conclusion: The authors concluded that the changes in exposed workers suggest potential inflammatory responses and cellular changes due to occupational exposure.
• Limitations the authors state:
  • The study was limited to one region, which might affect generalizability to other populations.
  • Only construction workers were studied, so effects in other occupations or the general population may be missed.
  • Unaccounted variables such as lifestyle habits or genetic predispositions may have influenced the results.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Inflammation, naturally occurring asbestos (NOA), Asbestiform, Chrysotile, Amphibole Group, Carcinogenic, Pleural Mesothelioma.

Related studies

• Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population — M. Yu, Y. Zhang, et al. (2015)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)
• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial — S.I. Katz, L. Roshkovan, et al. (2021)
• Mesothelin Gene Variants Affect Soluble Mesothelin-Related Protein Levels in the Plasma of Asbestos-Exposed Males and Mesothelioma Patients from Germany — H.P. Rihs, S. Casjens, et al. (2022)
• A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels — E.K. Park, D. Wilson, et al. (2012)

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