Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis

Our plain-English summary of Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis, by A. Cui, X.G. Jin, K. Zhai, et al (BMJ Open, 2014).

The study

• Authors: A. Cui, X.G. Jin, K. Zhai, Z.H. Tong, H.Z. Shi
• Journal: BMJ Open
• Published: 2014;4(2):e004145
• Type of article: Meta-analysis, Systematic review
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Although the values of soluble mesothelin-related peptides (SMRPs), including mesothelin and megakaryocyte potentiating factor, in serum and/or pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been extensively studied, the exact diagnostic accuracy of these SMRPs remains controversial. The purpose of the present meta-analysis is to update the overall diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic accuracy of SMRPs in pleural fluid for MPM.

Design: Systematic review and meta-analysis.

Methods: A total of 30 articles of diagnostic studies were included in the current meta-analysis. Sensitivity, specificity and other measures of accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.

Results: The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was also found that megakaryocyte potentiating factor in serum had a superior diagnostic accuracy compared with mesothelin for MPM.

Conclusions: SMRPs in both serum and pleural fluid are helpful markers for diagnosing MPM with similar diagnostic accuracy. The negative results of SMRP determinations are not sufficient to exclude non-MPM, and the positive test results indicate that further invasive diagnostic steps might be necessary for the diagnosis of MPM.

In plain English

In this systematic review and meta-analysis, the authors pooled 30 published articles found in MEDLINE and EMBASE up to 28 November 2013. These tested soluble mesothelin-related peptides (SMRPs: mesothelin and megakaryocyte potentiating factor, MPF) for diagnosing malignant pleural mesothelioma (MPM). Serum studies included 1562 patients with MPM and 5988 without; pleural fluid studies included 460 with MPM and 1046 without. In serum, pooled sensitivity was 0.61 (95% CI 0.58 to 0.63) and specificity 0.87 (95% CI 0.86 to 0.88). In pleural fluid, pooled sensitivity was 0.79 (95% CI 0.75 to 0.83) and specificity 0.85 (95% CI 0.83 to 0.87). Serum MPF performed better than serum mesothelin. Serum SMRPs separated MPM from healthy people better than from other cancers. The authors found signs of possible publication bias and noted varied control groups and cut-off values. The authors concluded that serum and pleural fluid SMRPs are helpful markers with similar accuracy. In their view, a negative result is not enough to rule out MPM, and a positive result suggests further invasive diagnostic steps might be necessary.

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 with random effects models
• Who was studied: 30 published English-language articles found in MEDLINE and EMBASE up to 28 November 2013. Serum studies: 1562 patients with MPM and 5988 non-MPM subjects. Pleural fluid studies: 460 patients with MPM and 1046 non-MPM subjects.
• Exposure: No asbestos exposure was analysed as such. The article evaluated diagnostic tests: mesothelin and megakaryocyte potentiating factor (MPF) measured in serum (28 study datasets) and pleural fluid (12 study datasets). Asbestos-exposed people were one of the comparison groups in subgroup analyses.
• Main results:
  • Serum SMRPs (28 studies): pooled sensitivity 0.61 (95% CI 0.58 to 0.63) and pooled specificity 0.87 (95% CI 0.86 to 0.88)
  • Serum SMRPs: positive likelihood ratio 5.71 (95% CI 4.28 to 7.62), negative likelihood ratio 0.43 (95% CI 0.38 to 0.50), diagnostic odds ratio 14.43 (95% CI 9.98 to 20.87)
  • Pleural fluid SMRPs (12 studies): pooled sensitivity 0.79 (95% CI 0.75 to 0.83) and pooled specificity 0.85 (95% CI 0.83 to 0.87)
  • Pleural fluid SMRPs: positive likelihood ratio 4.78 (95% CI 3.52 to 6.50), negative likelihood ratio 0.30 (95% CI 0.24 to 0.36), diagnostic odds ratio 19.50 (95% CI 12.14 to 31.33)
  • Area under the summary ROC curve was 0.806 for serum SMRPs and 0.890 for pleural fluid SMRPs
  • In serum, MPF performed better than mesothelin. Table 3 gives specificity 0.96 for MPF vs 0.85 for mesothelin, AUC 0.941 vs 0.785, and sensitivity 0.62 for both.
  • Serum SMRPs distinguished MPM from other cancers less well than from healthy controls or asbestos-exposed people. Table 4 gives diagnostic odds ratios of 69.27 vs healthy controls, 5.62 vs other cancers, and 18.03 vs benign asbestos-related diseases.
  • In pleural fluid, mesothelin's accuracy for separating MPM from other cancers was similar to its accuracy for separating MPM from benign pleural effusions
  • Egger tests indicated possible publication bias for both serum (p=0.038) and pleural fluid (p=0.035) studies
• The authors' conclusion: The authors concluded that SMRPs in serum and pleural fluid are helpful markers for diagnosing MPM, with similar accuracy. In their view, negative results are not sufficient to exclude MPM, and positive results indicate further invasive diagnostic steps might be necessary.
• Limitations the authors state:
  • Conference abstracts, letters to the editors and non-English studies were excluded, which the authors said may have led to publication bias
  • Studies reporting positive results are more likely to be published, which may inflate the accuracy estimates
  • Pathological types of MPM were not specified in three studies
  • 69.9% (982/1404) of MPM cases were epithelioid. The authors noted SMRP levels are higher in this subtype, which could partly explain the low sensitivity.
  • Control groups were very heterogeneous between studies
  • Different studies used different cut-off points

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), Pleural Mesothelioma, Meta-Analysis, Mesothelin, Systematic Review.

Related studies

• Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis — L. Luo, H.Z. Shi, et al. (2010)
• 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)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• 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) - high stability of a potential tumor marker for mesothelioma — D.G. Weber, D. Taeger, et al. (2007)
• Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma — A. Scherpereel, B. Grigoriu, et al. (2006)

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