Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions

Our plain-English summary of Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions, by H.I. Pass, A. Wali, N. Tang, et al (The Annals of Thoracic Surgery, 2008).

The study

• Authors: H.I. Pass, A. Wali, N. Tang, A. Ivanova, S. Ivanov, M. Harbut, M. Carbone, J. Allard
• Journal: The Annals of Thoracic Surgery
• Published: 2008;85(1):265-72; discussion 272
• Cited by: 110 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Soluble mesothelin-related peptide (SMRP) is a potential marker for malignant pleural mesothelioma (MPM), which may be useful for screening high-risk asbestos-exposed individuals.

Methods: We evaluated SMRP in serum from MPM patients (n = 90), lung cancer patients (n = 170), age and tobacco-matched asbestos-exposed individuals (n = 66), and in MPM pleural effusions (n = 45), benign effusions (n = 30), and non-MPM effusions (n = 20) using the MesoMark enzyme-linked immunosorbent assay kit (Fujirebio Diagnostics, Malvern, PA). Receiver operating characteristic (ROC) curves were used to define true and false positive rates at various cutoffs.

Results: Mean serum SMRP levels were higher in MPM compared with lung cancer (5.67 +/- 0.82 nM [mean +/- standard error of the mean vs 1.99 +/- 0.43 nM, p < 0.001), and stage I MPM SMRP levels (n = 12; 2.09 +/- 0.41 nM) were significantly higher than those in asbestos-exposed individuals (0.99 +/- 0.09 nM, p = 0.02, respectively). Stage 2 to 4 SMRP serum levels were significantly higher than those for stage 1 MPM. The area under the ROC curve for serum SMRP was 0.81 for differentiating MPM and asbestos-exposed individuals; cutoff = 1.9 nM (sensitivity = 60%, specificity = 89%). The MPM pleural effusion SMRP was significantly higher than benign or other non-MPM pleural effusions (65.57 +/- 11.33 nM vs 27.46 +/- 11.25 nM [p = 0.003] and 18.99 +/- 7.48 nM [p = 0.044], respectively).

Conclusions: These data support SMRP as a promising marker for MPM in both serum and pleural effusion fluid, and justify prospective screening studies of SMRP in combination with other markers for screening of asbestos-exposed cohorts.

In plain English

The authors measured a blood marker called soluble mesothelin-related peptide (SMRP) with the MESOMARK test kit in stored samples. Serum came from 90 patients with malignant pleural mesothelioma, 170 lung cancer patients and 66 asbestos-exposed people in Michigan. Pleural effusion fluid came from 45 mesothelioma patients, 30 people with benign effusions and 20 with other cancers. Mean serum SMRP was 5.67 nM in mesothelioma, 1.99 nM in lung cancer and 0.99 nM in the asbestos-exposed group. Stage I mesothelioma (2.09 nM) was higher than the asbestos-exposed group, and later stages were higher still. At a cutoff of 1.9 nM, the test flagged 60% of mesothelioma patients and correctly cleared 89.2% of asbestos-exposed people. In effusion fluid, the mean was 65.57 nM in mesothelioma, 18.99 nM in benign effusions and 27.46 nM in other cancers. The authors concluded that SMRP was a promising marker that justified prospective screening studies of SMRP combined with other markers in asbestos-exposed cohorts. They noted that the samples were not collected prospectively, the asbestos-exposed group was small and the effusion data were very preliminary.

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 marker study comparing SMRP levels (MESOMARK assay) between groups, using previously collected, stored serum and pleural effusion samples
• Who was studied: Serum from 90 malignant pleural mesothelioma patients and effusions from 45, collected 1990 to 2005 at the National Cancer Institute (Bethesda) or Karmanos Cancer Institute (Detroit). Serum from 170 lung cancer patients (120 from Karmanos, 50 from Fujirebio archives). Serum from 66 asbestos-exposed individuals at the Center for Occupational and Environmental Medicine, Royal Oak, Michigan, July to September 2004. Serum from 409 normal individuals. Effusions from 30 people with benign conditions and 20 with non-mesothelioma malignant effusions.
• Exposure: The comparison group had a history of asbestos exposure and/or radiographic changes; fiber types were not specified. Of 62 with complete information, 49 (79%) had worked five years or more in an asbestos-related trade. Fibrosis was seen in 18 of 62 (29%) and pleural plaques in 40 of 62 (65%). Among mesothelioma patients, 73 of 90 (81%) had asbestos exposure.
• Main results:
  • Mean serum SMRP was 5.67 nM in the 90 mesothelioma patients. This was significantly higher than in lung cancer patients (1.99 nM) and in asbestos-exposed individuals (0.99 nM).
  • Serum SMRP in lung cancer patients was not significantly different from the asbestos-exposed group (p 0.173).
  • Stage I mesothelioma patients had higher serum SMRP than the asbestos-exposed group: 2.09 vs 0.99 nM, p 0.02.
  • Mesothelioma stages above stage I had significantly higher serum SMRP (10.61 nM, p 0.03) than stage I.
  • Serum SMRP was not an independent predictor of survival in the mesothelioma patients (Cox proportional hazards model).
  • For telling mesothelioma apart from asbestos-exposed individuals, the area under the ROC curve was 0.810 (95% CI 0.739 to 0.868). At the best cutoff of 1.9 nM, specificity was 89.2%, sensitivity 60% and accuracy 73%.
  • For mesothelioma vs lung cancer, the area under the curve was 0.820 (95% CI 0.768 to 0.865). At a 1.1 nM cutoff, specificity was 76.4% and sensitivity 78.9%.
  • For stage I mesothelioma vs asbestos-exposed individuals, the area under the curve was 0.741 (95% CI 0.630 to 0.834). At a 2.0 nM cutoff, specificity was 91% and sensitivity 58%.
  • The 409 normal individuals had lower serum SMRP than the 66 asbestos-exposed individuals (0.39 vs 0.99). After matching for age and sex, the difference was smaller but still significant (0.65 vs 0.89, p 0.01).
  • Among asbestos-exposed individuals, serum SMRP did not differ by age, sex or exposure duration.
  • Serum SMRP did not differ between epithelial (n 58, 5.88 nM) and biphasic (n 29, 5.64 nM) mesothelioma.
  • Mean pleural effusion SMRP was 65.57 nM in mesothelioma. This was higher than in benign effusions (18.99 nM, p 0.003) and in effusions from other cancers (27.46 nM, p 0.044).
  • For mesothelioma effusions vs all other effusions, the area under the curve was 0.76 (95% CI 0.662 to 0.842). At a 12.6 nM cutoff, sensitivity was 75.6% and specificity 82%.
  • Raising serum sensitivity to 95% (cutoff 0.36 nM) would lower specificity to 17%.
• The authors' conclusion: The authors concluded that the data support SMRP as a promising marker for malignant pleural mesothelioma in both serum and pleural effusion fluid. In their view, this justifies prospective screening studies of SMRP in combination with other markers in asbestos-exposed cohorts.
• Limitations the authors state:
  • The samples were collected in the past rather than prospectively, so the groups may not be representative.
  • The asbestos-exposed population was small.
  • The pleural effusion data should be considered very preliminary.
  • Important benign causes of effusion (such as organ failure, infection and autoimmune conditions) were not well represented.
  • Most of the cancer effusions were lung adenocarcinoma.
  • There were too few pure sarcomatoid cases to draw conclusions about that subtype.
  • For early detection, sensitivity would need to be close to 100%, which the serum test did not reach at acceptable specificity.

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, Pleural Effusion, Soluble Mesothelin-Related Peptides (SMRP), Pleural Mesothelioma, Lung Cancer.

Related studies

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• Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure — J.A. Rodríguez Portal, E. Rodríguez Becerra, et al. (2009)
• 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)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma — B.M. Burt, H.S. Lee, et al. (2017)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)

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