Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis

Our plain-English summary of Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis, by L. Luo, H.Z. Shi, Q.L. Liang, et al (Respiratory Medicine, 2010).

The study

• Authors: L. Luo, H.Z. Shi, Q.L. Liang, J. Jiang, S.M. Qin, J.M. Deng
• Journal: Respiratory Medicine
• Published: 2010;104(1):149-56
• Type of article: Meta-analysis, Systematic review
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Serum concentrations of soluble mesothelin-related peptides (SMRP) have been reported to be higher in patients with malignant mesothelioma than in healthy subjects and in patients with non-malignant mesothelioma diseases. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of the measurement of SMRPs for diagnosing malignant mesothelioma.

Methods: After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of serum SMRPs in the diagnosis of malignant mesothelioma were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance.

Results: Eleven publications from 12 studies met our inclusion criteria. The summary estimates for SMRPs in the diagnosis of malignant mesothelioma in the studies included were sensitivity 0.64 (95% confidence interval 0.61-0.68), specificity 0.89 (0.88-0.90), positive likelihood ratio 7.10 (4.44-11.35), negative likelihood ratio 0.39 (0.31-0.48), and diagnostic odds ratio 19.35 (10.95-34.17).

Conclusions: Serum SMRP determination plays a role in the diagnosis of malignant mesothelioma. The results of SMRP assays should be interpreted in parallel with clinical findings and the results of conventional tests.

Copyright 2009 Elsevier Ltd. All rights reserved.

In plain English

This was a meta-analysis. The authors pooled results from earlier published studies rather than testing patients themselves. They asked how accurately a blood test for soluble mesothelin-related peptides (SMRP) identifies malignant mesothelioma. They searched medical databases up to March 8, 2008, and included 11 English-language publications reporting 12 studies. These covered 717 people with mesothelioma and 2851 people without it. Some comparison groups were asbestos-exposed people or patients with benign asbestos-related disease. Pooled across studies, the test was positive in 64% of mesothelioma patients (sensitivity 0.64, 95% confidence interval 0.61 to 0.68). It was negative in 89% of people without mesothelioma (specificity 0.89, 0.88 to 0.90). Results differed significantly between studies. The test did less well at telling mesothelioma apart from other lung diseases than from healthy people. The authors judged overall accuracy (area under the curve 0.82) "not as high as expected" and found signs of possible publication bias. They concluded that the test plays a role in diagnosing malignant mesothelioma, but that results should be interpreted alongside clinical findings and conventional tests.

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: Systematic review and meta-analysis of published diagnostic accuracy studies, pooled using random-effects models
• Who was studied: 11 English-language publications (12 studies), with study sizes from 83 to 1086 subjects. Together they included 717 patients with malignant mesothelioma and 2851 people without it. Comparison groups varied: healthy controls with and without asbestos exposure, patients with benign asbestos-related diseases, lung cancer, other cancers and other lung diseases. Databases were searched up to March 8, 2008.
• Exposure: Serum (blood) levels of soluble mesothelin-related peptides, measured by enzyme-linked immunosorbent assay. Eight publications measured soluble mesothelin and three measured soluble megakaryocyte potentiating factor. Cut-off values differed between studies. Asbestos exposure was not the variable studied.
• Main results:
  • Pooled sensitivity across the 12 studies was 0.64 (95% CI 0.61 to 0.68). Individual studies ranged from 0.41 to 0.91.
  • Pooled specificity was 0.89 (95% CI 0.88 to 0.90). Individual studies ranged from 0.73 to 1.00.
  • Pooled positive likelihood ratio was 7.10 (95% CI 4.44 to 11.35). Negative likelihood ratio was 0.39 (0.31 to 0.48). Diagnostic odds ratio was 19.35 (10.95 to 34.17).
  • There was significant heterogeneity between studies for all accuracy measures (all p less than 0.001).
  • Summary curve analysis gave a maximum joint sensitivity and specificity of 0.76 and an area under the curve of 0.82. The authors described this overall accuracy as not as high as expected.
  • In a hypothetical patient with a 10% pre-test probability, a positive result gave an estimated post-test probability of 43.8% and a negative result 3.8%. At 25% pre-test probability the figures were 70.1% (positive) and 11.5% (negative). At 50% they were 87.7% (positive) and 28.1% (negative).
  • Mesothelioma versus healthy controls (7 studies): sensitivity 0.64, specificity 0.92, area under the curve 0.85. Mesothelioma versus other lung diseases (7 studies): sensitivity 0.61, specificity 0.90, area under the curve 0.77. The authors said the test did not perform as well against other pulmonary diseases.
  • The Egger test was significant (p equal to 0.018) and the funnel plot was asymmetric, indicating potential publication bias.
• The authors' conclusion: The authors concluded that serum SMRP measurement plays a role in diagnosing malignant mesothelioma. They added that results should be interpreted together with clinical findings and conventional tests. They also noted that its accuracy resembles that of conventional tests such as cytology (high specificity, low sensitivity), which might make it less useful in practice.
• Limitations the authors state:
  • Conference abstracts were excluded, which may have led to publication bias, and publication bias was observed.
  • Only English-language articles were reviewed in full.
  • The way mesothelioma was diagnosed varied between studies, and some patients were diagnosed on cytology alone.
  • Control groups were very heterogeneous across studies, which may have affected test performance.
  • There were too few studies to assess whether study quality or design affected accuracy.

Topics

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

Medical terms in this study, explained in our Lexicon: Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Meta-Analysis, Systematic Review, confidence interval, Odds Ratio.

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