Soluble mesothelin-related protein--a blood test for mesothelioma

Our plain-English summary of Soluble mesothelin-related protein--a blood test for mesothelioma, by B.W. Robinson, J. Creaney, R. Lake, et al (Lung Cancer, 2005).

The study

• Authors: B.W. Robinson, J. Creaney, R. Lake, A. Nowak, A.W. Musk, N. de Klerk, P. Winzell, K.E. Hellstrom, I. Hellstrom
• Journal: Lung Cancer
• Published: 2005;49 Suppl 1:S109-11
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM.

In plain English

This short report summarized the authors' earlier study of whether a blood protein, soluble mesothelin-related protein (SMRP), could mark mesothelioma. Serum samples came from 48 mesothelioma patients and 228 comparison people. These included healthy adults with and without asbestos exposure and patients with other lung, pleural and cancer conditions. SMRP was elevated in 40 of the 48 patients, a sensitivity of 83% (95% CI 73% to 93%). Only 10 of 228 comparison samples were positive, 7 of them from asbestos-exposed healthy people. Specificity was 100% (95% CI 91% to 100%) against other pleural diseases (38 of 38), 95.4% (CI 84% to 100%) against other lung tumors (21 of 22) and 82.5% (CI 70% to 93%) against asbestos-exposed subjects (33 of 40). Levels were significantly lower with smaller tumors, fell after surgical removal of tumor and rose with progression. Seven asbestos-exposed controls had elevated SMRP, and 3 of them developed mesothelioma 1 to 5 years later. None of the other 33 did in 8 years of follow-up. The authors concluded serum SMRP should help diagnose and monitor mesothelioma, while noting their numbers were limited.

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: Diagnostic test evaluation of a blood test (SMRP ELISA) in mesothelioma patients and comparison groups. It is a brief report summarizing the authors' previously published study (Lancet 2003).
• Who was studied: 48 patients with mesothelioma and 228 comparison subjects. The comparison subjects were 28 healthy adults with no history of asbestos exposure, 40 healthy age-matched adults with documented asbestos exposure, 92 patients with inflammatory lung diseases (including 22 with asbestosis), 30 with non-mesothelioma cancers without pleural involvement, 20 with non-mesothelioma pleural effusions, and 18 with other non-malignant pleural diseases (16 with localised asbestos-related pleural plaques, 2 with gross diffuse pleural thickening). The study was approved by ethics committees in Western Australia; dates were not given.
• Exposure: Not an exposure study. Documented asbestos exposure defined one healthy control group; no fiber types, products, jobs or doses were described. The test studied was serum SMRP measured by a double determinant ELISA using two antibodies (OV569 and 4H3).
• Main results:
  • SMRP was elevated in 40 of 48 patients with established mesothelioma, compared with asbestos-exposed and non-asbestos-exposed controls (p less than 0.001 for each).
  • Sensitivity for mesothelioma was 83% (95% CI 73%, 93%).
  • Only 10 of the 228 comparison sera were positive, and 7 of these were in the asbestos-exposed healthy group.
  • Specificity was 100% (95% CI 91%, 100%) compared with other pleural diseases (38/38).
  • Specificity was 95.4% (95% CI 84%, 100%) compared with other lung tumors (21/22), and 82.5% (95% CI 70%, 93%) compared with other asbestos-exposed subjects (33/40).
  • SMRP levels were significantly lower with smaller tumors (p less than 0.001). The assay detected 15 of 21 of the smallest tumors.
  • Among 40 healthy asbestos-exposed controls followed with annual serum samples, 7 had elevated SMRP, and 3 of these developed mesothelioma 1 to 5 years later. None of the other 33, whose SMRP was normal, developed mesothelioma in 8 years of follow-up.
  • In mesothelioma patients, SMRP levels fell after surgical resection and rose again with progression.
• The authors' conclusion: The authors concluded that measuring serum SMRP should help in the diagnosis and monitoring of mesothelioma. They suggested it could be monitored in asbestos-exposed people at risk, to test whether early intervention improves outcome.
• Limitations the authors state:
  • The 100% specificity against other pleural diseases rested on limited numbers, and the authors did not expect it to hold up in larger studies.

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, Mesothelioma, Tumor Marker, Soluble Mesothelin-Related Peptides (SMRP), Disease Progression.

Related studies

• Mesothelin-family proteins and diagnosis of mesothelioma — B.W. Robinson, J. Creaney, et al. (2003)
• Soluble mesothelin-related protein in an asbestos-exposed population: the dust diseases board cohort study — E.K. Park, A. Sandrini, et al. (2008)
• Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population — E.K. Park, P.S. Thomas, et al. (2010)
• 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)
• 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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