Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population

Our plain-English summary of Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population, by M. Yu, Y. Zhang, Z. Jiang, et al (Environmental Health and Preventive Medicine, 2015).

The study

• Authors: M. Yu, Y. Zhang, Z. Jiang, J. Chen, L. Liu, J. Lou, X. Zhang
• Journal: Environmental Health and Preventive Medicine
• Published: 2015;20(5):369-78
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: This study investigated the mesothelin (MSLN) methylation and its relationship with soluble mesothelin-related protein (SMRP) levels in participants stratified by asbestos exposure scenarios and benign asbestos-related diseases (ARDs).

Methods: The presence of benign ARDs was confirmed through chest X-ray and the asbestos exposure history was obtained using a standardized questionnaire in this study, including 262 participants. Sera SMRP were measured using MESOMARK, and MSLN methylation in genomic DNA extracted from whole blood was detected by real-time methylation-specific PCR. Covariates were compared with SMRP concentrations using correlation analysis and the potential covariates affecting SMRP were determined by multiple linear regression analysis, and the distribution of methylation status was analyzed by Chi-square test.

Results: There was a trend toward elevation of SMRP values in healthy individuals exposed to asbestos as compared with those without asbestos exposure. The highest median level of SMRP was 1.3 nM in subjects with asbestosis, followed by cases with pleura plaque and asbestosis (1.2 nM), pleura plaque (0.9 nM), healthy subjects with occupational exposure (0.9 nM), non-occupational exposure (0.8 nM), and mixed exposure (0.8 nM). Within asbestosis cases, those with higher profusion scores had higher SMRP values than those with lower profusion scores (1.6 vs. 0.8 nM). Based on multi-regression analysis, the trend toward elevation of SMRP remained significant in subjects with occupational exposure or in those with asbestosis, as compared with healthy subjects without exposure (p < 0.01), although body mass index had an effect on SMRP (p < 0.0001). Regardless of the differences in SMRP levels among these subgroups, MSLN methylation ranged from 80.5 to 92.5 %, with no significant difference. The elevated level of SMRP in asbestosis with higher profusion scores could not be attributed to low MSLN methylation status.

Conclusions: Our findings suggest that the elevation of SMRP is related to asbestos exposure and benign ARDs especially for cases with high profusion scores, which is independent of MSLN methylation.

In plain English

This study measured soluble mesothelin-related protein (SMRP) in blood from 262 people in Yuyao and Cixi, China, an asbestos-product manufacturing area since the 1950s. It also measured mesothelin gene methylation (a chemical marking) in blood DNA from 124 samples. Groups were unexposed healthy people, healthy people with non-occupational, occupational or mixed exposure, and people with X-ray-read asbestosis, pleural plaque, or both. People with asbestosis alone had the highest median SMRP, 1.3 nM. After adjusting for age, body mass index, kidney function and other factors, SMRP stayed significantly higher than in unexposed healthy people only for occupationally exposed healthy people and people with asbestosis (with or without plaque). Body mass index was independently linked to SMRP. In healthy people with occupational or mixed exposure, SMRP did not significantly correlate with exposure duration or estimated exposure level. Asbestosis cases with clearly abnormal X-ray scores had higher median SMRP than intermediate cases (1.62 vs 0.8 nM). Of the 124 samples, 111 were fully methylated, with no significant group differences. The authors concluded the SMRP increases were independent of methylation at the tested gene sites. They noted blood DNA may not reflect lung or pleural cells.

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: Cross-sectional biomarker study comparing groups defined by asbestos exposure history and chest X-ray findings
• Who was studied: 262 residents of the Yuyao and Cixi area, China, where asbestos-product manufacturing had existed since the 1950s. There were seven groups: healthy unexposed (n = 45), healthy non-occupationally exposed only (n = 27), healthy occupationally exposed only (n = 56), healthy with mixed exposure (n = 40), asbestosis and pleural plaque (n = 26), asbestosis only (n = 17), and pleural plaque only (n = 51). Methylation was reported for 124 samples.
• Exposure: Asbestos exposure from asbestos textile production in household textile workshops and large textile manufactories. Occupational exposure meant working in asbestos-product manufacturing. Non-occupational exposure meant living near the plants or having family members who handled asbestos. Fiber type was not stated. Total dust data from 1984 to 2010 gave a median of 0.7 mg/m3 (interquartile 0.4 to 1.0) in household workshops and 5.9 mg/m3 (2.5 to 13.2) in textile manufactories. Exposure duration was recorded only for occupationally exposed participants. Mean exposure duration in the occupationally exposed groups ranged from 8.0 to 10.8 years.
• Main results:
  • Across all 262 participants, 21 sera (8.0%) were below the 0.3 nM detection limit and were assigned 0.3 nM. The overall median SMRP was 0.87 nM (interquartile 0.55 to 1.54).
  • The highest median SMRP, 1.3 nM, was in group 6 (asbestosis only), and it was significantly higher than in group 1 (healthy unexposed).
  • Before adjustment, SMRP in group 3 (healthy occupationally exposed), group 5 (asbestosis and plaque) and group 7 (plaque only) was also higher than in group 1 (p less than 0.05).
  • In multiple linear regression adjusting for covariates, SMRP in healthy occupationally exposed subjects (group 3) remained significantly higher than in healthy unexposed subjects (p = 0.007).
  • After adjustment, SMRP remained significantly higher than in healthy unexposed subjects for cases with asbestosis and pleural plaque (group 5, p less than 0.0001) and for subjects with asbestosis only (group 6, p = 0.002). Group 2 (p = 0.812), group 4 (p = 0.151) and group 7 (p = 0.112) were not significantly different.
  • Body mass index was independently associated with SMRP (inversely; p less than 0.0001). Smoking had no effect on SMRP in the regression.
  • In apparently healthy participants with occupational or mixed asbestos exposure (the groups for whom exposure duration was recorded), SMRP was not significantly correlated with exposure duration (Spearman r = -0.001333, p = 0.9899) or with estimated exposure level (Spearman r = 0.02963, p = 0.7865).
  • Among asbestosis cases, median SMRP was lower in those with intermediate profusion scores than in those rated clearly abnormal (0.8 vs. 1.62 nM, p less than 0.05). There was no significant difference in SMRP by extent of pleural plaque.
  • In group 6 (asbestosis only), median SMRP was higher in those occupationally exposed than in those with mixed exposure: 1.8 (1.0, 2.5) vs 0.7 (0.4, 1.2) nM, p = 0.0129.
  • Of 124 blood samples, 111 (89.5%) were fully methylated at the MSLN promoter, 11 (8.9%) were partially methylated and 2 (1.6%) were unmethylated, a low-methylation rate of 10.5%.
  • Low methylation was found in 18.2% (4/22) of healthy unexposed individuals, 7.5% (3/40) of occupationally exposed participants and 9.5% (6/63) of those with non-malignant asbestos-related diseases. The difference was not significant (p = 0.4117).
  • Low methylation was found in 5.9% (2/34) of asbestosis subjects and 13.8% (4/29) of pleural plaque subjects, with no significant difference (p = 0.3463).
• The authors' conclusion: The authors concluded that SMRP levels were significantly increased in occupationally exposed subjects and in patients with non-malignant asbestos-related diseases after taking clinical and demographic variables into account. They concluded this was independent of MSLN methylation status at the CpG sites they probed.
• Limitations the authors state:
  • DNA from whole blood is a mixture of different white blood cell types and may not reflect specific tissues such as mesothelial cells. The authors could not give a definitive explanation of how methylation in lung or pleural tissue affects SMRP.
  • Only a limited number of CpG sites were analyzed, so the methylation findings might not fully explain epigenetic effects on MSLN products.
  • Non-occupationally exposed subjects had difficulty recalling exposure duration, so no exposure duration or exposure level was quantified for them.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Asbestos Exposure, Chest X-Ray, Pleura, Occupational Exposure, Non-Occupational Exposure.

Related studies

• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• A common polymorphism within MSLN affects miR-611 binding site and soluble mesothelin levels in healthy people — S. Garritano, C. De Santi, et al. (2014)
• Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases — K. Goricar, V. Kovac, et al. (2020)
• The relationship between tumor MSLN methylation and serum mesothelin (SMRP) in mesothelioma — H.H. Nelson, L.M. Almquist, et al. (2011)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)
• Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers — C. Ledda, C. Loreto, et al. (2024)

Browse more research in Environmental Health and Preventive Medicine, or return to medical research.