A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels

Our plain-English summary of A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels, by E.K. Park, D. Wilson, D.H. Yates (Clinical Chemistry and Laboratory Medicine, 2012).

The study

• Authors: E.K. Park, D. Wilson, D.H. Yates
• Journal: Clinical Chemistry and Laboratory Medicine
• Published: 2012;50(12):2199-204
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant mesothelioma (MM) is an aggressive pleural tumor which is difficult to diagnose in its early stages. Thus, biomarkers for MM including soluble mesothelin-related protein (SMRP) are currently an area of intense research interest. However, SMRP is affected by several factors other than malignancy which need to be taken into account in the individual patient. This study aimed to evaluate factors required to adjust SMRP levels for such variables and produce a useful prediction equation for clinical application.

Methods: Serum SRMP levels were measured in 535 subjects formerly exposed to asbestos and silica, including many with asbestos-related disorders (ARDs). Linear regression analyses were used to quantify the strength and “ direction ” of the relationship between SMRP and several independent variables,and 2 × 2 tables were used to determine the diagnostic accuracy of SMRP levels, taking into account clinical variables.

Results: SMRP levels were affected by age and glomerular filtration rate (GFR), which were strong confounders in this study. Body mass index (BMI) was also an initial confounder but lost significance after other factors were taken into account.SMRP was also affected by smoking. Poor sensitivity (15.1 % )for SMRP values among subjects with non-malignant asbestos-related disorders was found when compared to currently healthy subjects with a history of asbestos exposure.

Conclusions: The present study proposes an equation based on age and GFR to improve diagnostic accuracy of SMRP.The poor sensitivity of SMRP found in this study suggests that further work is needed to fi nd new candidate biomarkers for diagnosing early stage MM.

In plain English

This study measured soluble mesothelin-related protein (SMRP), a blood marker studied as a possible test for malignant mesothelioma, in 535 people with past asbestos and silica exposure attending the Workers' Compensation (Dust Diseases) Board, Sydney, Australia. They were 223 currently healthy asbestos-exposed people and people with asbestosis, diffuse pleural thickening, both, pleural plaques or silicosis. No mesothelioma group was listed. Older age and lower kidney function (estimated GFR) were linked to higher SMRP. Body mass index lost statistical significance once these were included. After adjustment, people with GFR below 45 mL/min had an odds ratio for high SMRP of 3.73 (95% CI 1.29 to 10.79) compared with GFR above 80. People with more than 26 pack-years of smoking had an adjusted odds ratio for high SMRP of 2.38 (95% CI 1.13 to 5.03) compared with never-smokers. No clear dose-dependent pattern was seen across smoking categories. The authors proposed an equation based on age and GFR. At a 1.5 nmol/L cut-off, SMRP was high in 15.1% of 292 people with non-malignant asbestos-related disorders (sensitivity). Specificity, measured in the healthy group, was 92.8%. Neither figure measures detection of mesothelioma. The authors urged extreme caution in using the test clinically.

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: Analysis of SMRP blood levels and clinical factors in subjects already recruited into a prospective study of SMRP, using logistic and linear regression and 2 × 2 tables for diagnostic accuracy
• Who was studied: 535 subjects with a history of asbestos and silica exposure attending the Workers' Compensation (Dust Diseases) Board, Sydney, Australia. The groups were 223 currently healthy people with a history of asbestos exposure, 24 with asbestosis, 113 with diffuse pleural thickening, 13 with asbestosis plus diffuse pleural thickening, 142 with pleural plaques, and 20 with silicosis. Mean age was 66.9 years and 526 (98.3%) were male.
• Exposure: Past asbestos and silica exposure (fiber types not specified). Serum SMRP was measured with the Mesomark ELISA kit, and a level of 1.5 nmol/L or more was classed as high.
• Main results:
  • In linear regression including BMI, age (p = 0.0098) and estimated GFR (p = 0.0013) remained statistically significant predictors of SMRP, but BMI did not (p = 0.0783)
  • Proposed equation: SMRP level = (0.0076 × Age) minus (0.00462 × estimated GFR) plus 0.70421. The model was statistically significant (p less than 0.0001).
  • Subjects with GFR below 45 mL/min, compared with GFR above 80 mL/min, had an unadjusted odds ratio for high SMRP of 6.53 (95% CI 2.60 to 16.43) and an adjusted odds ratio of 3.73 (1.29 to 10.79)
  • Subjects over 75, compared with under 60, had an unadjusted odds ratio for high SMRP of 5.20 (2.06 to 13.11). After adjustment it was 1.94 (0.67 to 5.60), and statistical significance was lost.
  • Subjects with more than 26 pack-years of smoking, compared with never-smokers, had an unadjusted odds ratio for high SMRP of 2.78 (95% CI 1.34 to 5.75) and an adjusted odds ratio of 2.38 (95% CI 1.13 to 5.03)
  • The authors did not see a clear dose-dependent increase in odds ratios across smoking pack-year categories
  • Compared with apparently healthy subjects, the unadjusted odds ratios for high SMRP were 2.41 (1.12 to 10.32) for subjects with asbestosis and 1.90 (1.49 to 5.63) for subjects with pleural plaques. After adjustment they were 1.59 (0.49 to 5.20) and 1.56 (0.75 to 3.21), which were not statistically significant.
  • Compared with the 223 healthy asbestos-exposed subjects, specificity was 92.8% and sensitivity by disease group ranged from 5.0% (silicosis) to 20.8% (asbestosis). Sensitivity was 10.6% for diffuse pleural thickening, 7.7% for asbestosis plus diffuse pleural thickening, and 18.3% for pleural plaques.
  • For all non-malignant asbestos-related disorder groups combined, excluding silicosis (n = 292), sensitivity was 15.1%, specificity 92.8%, positive predictive value 73.3% and negative predictive value 45.5%. Specificity was measured against the 223 currently healthy asbestos-exposed subjects.
• The authors' conclusion: The authors concluded that their equation should allow slightly better use of a single SMRP result, but that clinicians should apply extreme caution with the test. They also concluded that SMRP alone appears unlikely to fulfil its initial promise for early diagnosis of mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Biomarker, Asbestos Exposure.

Related studies

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• Is soluble mesothelin-related protein an upfront predictive marker of pleural mesothelioma? A prospective study on Italian workers exposed to asbestos — R. Filiberti, P. Marroni, et al. (2014)
• Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis — R. Gao, F. Wang, et al. (2019)
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• Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders — E.K. Park, A.R. Johnson, et al. (2020)

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