Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population

Our plain-English summary of Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population, by E.K. Park, P.S. Thomas, J. Creaney, et al (Clinical Chemistry and Laboratory Medicine, 2010).

The study

• Authors: E.K. Park, P.S. Thomas, J. Creaney, A.R. Johnson, B.W. Robinson, D.H. Yates
• Journal: Clinical Chemistry and Laboratory Medicine
• Published: 2010;48(6):869-74
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study.

Methods: Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations.

Results: The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001).

Conclusions: This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.

In plain English

This study measured soluble mesothelin-related protein (SMRP), a blood marker proposed for detecting malignant mesothelioma, in 538 people with a history of asbestos exposure. They were examined at the Workers' Compensation (Dust Diseases) Board of New South Wales in Sydney, Australia, as part of a screening study. Almost all (98.3%) were men, and their mean age was 66.9 years. Participants included 223 healthy exposed people and others with pleural plaques, diffuse pleural thickening, asbestosis or silicosis. Mean serum SMRP was 0.91 nmol/L. Higher SMRP was associated with older age and higher serum creatinine. Lower SMRP was associated with higher weight, body mass index, non-fasting blood glucose and estimated kidney filtration rate (eGFR). It was also associated with higher lung diffusing capacity (DLco and DLco/VA), expressed as percent of predicted values. SMRP was not linked to spirometry, height, blood pressure or respiratory symptoms. The authors noted three things: the correlations were generally low except for creatinine, the factors were probably interrelated, and their occupational histories could not assess exposure levels. The authors concluded that age, weight, BMI and kidney function should be taken into account when interpreting SMRP.

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 correlation analysis carried out within a prospective screening study for mesothelioma. SMRP was compared with other measurements using Pearson analysis and Student's t-test.
• Who was studied: 538 participants with a history of asbestos exposure, attending routine examinations at the Workers' Compensation (Dust Diseases) Board of New South Wales, Sydney, Australia. 98.3% were male (n=529) and 1.7% female (n=9); mean age was 66.9 years. Diagnostic groups: asbestosis (n=24), diffuse pleural thickening (n=113), asbestosis and diffuse pleural thickening (n=13), silicosis (n=20), silicosis and asbestosis (n=1), silicosis and diffuse pleural thickening (n=2), pleural plaques (n=142), and healthy but asbestos-exposed (n=223).
• Exposure: History of asbestos exposure. The article does not report fiber types, products, jobs or doses, and the authors state their occupational histories were not adequate to assess exposure levels.
• Main results:
  • Mean serum SMRP in all 538 participants was 0.91 (SD 0.67) nmol/L. Thirty-five sera (6.5%) were below the detection limit of 0.3 nmol/L and were assigned that value.
  • SMRP was positively associated with age (Pearson r = 0.2315, p less than 0.0001).
  • SMRP was inversely associated with weight (Pearson r = -0.1254, p = 0.0036) and BMI (Pearson r = -0.1594, p = 0.0002).
  • SMRP was positively associated with serum creatinine (Pearson r = 0.3833, p less than 0.0001).
  • SMRP was inversely associated with estimated glomerular filtration rate (eGFR) (Pearson r = -0.2835, p less than 0.0001).
  • SMRP was inversely associated with non-fasting serum glucose (Pearson r = -0.1515, p = 0.0004).
  • SMRP was inversely associated with DLco % predicted (Pearson r = -0.1847, p less than 0.0001) and DLco/VA % predicted (Pearson r = -0.1872, p less than 0.0001).
  • SMRP showed no correlation with percent-predicted FEV1 (p = 0.7805), FVC (p = 0.4725) or FEV1/FVC (p = 0.9358).
  • There was no significant correlation between SMRP and height (p = 0.2965), systolic blood pressure (p = 0.9983) or diastolic blood pressure (p = 0.0855). Mean SMRP did not differ significantly between hypertensive (n=148) and non-hypertensive (n=390) subjects: 0.87 and 0.92 nmol/L respectively.
  • There was no relationship between SMRP and MRC scales of exercise capacity, chest pain, cough or dyspnoea.
  • With a 2.5 nmol/L cut-off for an abnormal result, 15 values were abnormal, and correlations were significant only for creatinine and eGFR.
• The authors' conclusion: The authors concluded that demographic variables such as age, weight and BMI, as well as renal function, affected SMRP. They said this should be taken into account when interpreting circulating SMRP clinically, and if SMRP is considered as a screening tool for mesothelioma in asbestos-exposed workers.
• Limitations the authors state:
  • Correlation coefficients were generally low except for serum creatinine, so the clinical significance of individual factors is questionable.
  • The variables are likely interrelated.
  • Blood glucose was measured in non-fasting samples, so it could be affected by many factors, such as recent carbohydrate intake.
  • Occupational histories were not adequate to assess levels of asbestos exposure.
  • The male-female comparison is difficult to interpret because of the difference in sample size (529 men vs 9 women).

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Asbestos Exposure, EGFR, Diffusing Capacity (DLCO), Confounding.

Related studies

• Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study — E.K. Park, A. Sandrini, et al. (2008)
• 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)
• 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 protein--a blood test for mesothelioma — B.W. Robinson, J. Creaney, et al. (2005)
• Early detection of malignant pleural mesothelioma through measurement of soluble mesothelin-related protein and positron emission tomography — E.L. O'Lone, E.K. Park, et al. (2009)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)

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