Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis

Our plain-English summary of Diagnostic value of soluble mesothelin-related peptides in pleural effusion for malignant pleural mesothelioma: An updated meta-analysis, by R. Gao, F. Wang, Z. Wang, et al (Medicine, 2019).

The study

• Authors: R. Gao, F. Wang, Z. Wang, Y. Wu, L. Xu, Y. Qin, H. Shi, Z. Tong
• Journal: Medicine
• Published: 2019;98(14):e14979
• Type of article: Meta-analysis, Systematic review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Soluble mesothelin-related peptide (SMRP) is a widely studied tumor marker for diagnosing malignant pleural mesothelioma (MPM). This study discussed the diagnostic value of SMRPs in pleural effusion (PE) for MPM.

Methods: Medline, Embase, Web of Science, and Cochrane library system were systematically searched on the data of SMRPs in PE for MPM diagnosis. Pooled diagnostic sensitivity, specificity, and symmetric receiver operating characteristic curve were calculated.

Results: Thirteen studies fulfilled the inclusion criteria and a total of 3359 cases including 759 MPM cases, 1061 non-MM (malignant mesothelioma) malignant PE, and 1539 benign PE were brought into this meta-analysis. The pooled results of SMRPs in PE for diagnosing MPM were as follows: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.68 (95% confidence interval [CI]: 0.64-0.72), 0.91 (95% CI: 0.86-0.94), 7.8 (95% CI: 5.0-12.0), 0.35 (95% CI: 0.31-0.40), and 22 (95% CI: 14-35), respectively. The area under the summary receiver operating characteristic curves (AUC) was 0.75 (95% CI: 0.72-0.80). Subgroup analyzes revealed that the AUC of cohort group using histological diagnosis could be improved to 0.86 (95% CI: 0.83, 0.89). The Deek's funnel plot asymmetry test showed no publication bias.

Conclusion: Although the sensitivity of SMRPs was low, PE-SMRPs can be a good indicator of the existence of MPM.

In plain English

This systematic review and meta-analysis pooled earlier studies rather than testing new patients. The authors searched four databases up to August 24, 2018 for studies measuring soluble mesothelin-related peptides (SMRPs), a protein marker, in pleural effusion fluid to diagnose malignant pleural mesothelioma (MPM). Thirteen studies were included; the text dates them 2007 to 2017, but its table lists a 2006 study. Patient totals are given as 3356 (756 with MPM) and 3359. Pooled across all studies, sensitivity was 0.69 (95% CI 0.64 to 0.72), meaning about 69% of MPM cases were detected. Specificity was 0.90 (95% CI 0.85 to 0.94), meaning about 90% without MPM tested negative. The overall accuracy measure (AUC) was 0.75 (95% CI 0.72 to 0.80). Specificity varied widely between studies. In six cohort studies, excluding those relying on fluid cytology for diagnosis, the AUC was 0.86 (95% CI 0.83 to 0.89). The authors concluded that pleural fluid SMRPs can be a good indicator of MPM, with high levels supporting further invasive tests, but that sensitivity is too low for screening. The article did not examine asbestos exposure.

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 diagnostic accuracy studies (registered with PROSPERO)
• Who was studied: 13 published studies of patients with pleural effusion, from France, Italy, Australia, UK, Japan and the US. The text says the studies were published 2007 to 2017, but Table 1 and the reference list include a 2006 study. The article reports 3356 patients in one place: 756 with malignant pleural mesothelioma, 1061 with other malignant pleural effusions and 1539 with benign pleural effusions. It gives 3359 elsewhere. Databases were searched until August 24, 2018.
• Exposure: Not an asbestos exposure study. The test studied was the level of soluble mesothelin-related peptides measured in pleural effusion fluid. Most studies used ELISA and 2 used CLEIA, with cutoff values from 8 to about 24 nmol/L.
• Main results:
  • All 13 studies pooled: sensitivity 0.69 (95% CI 0.64 to 0.72) and specificity 0.90 (95% CI 0.85 to 0.94) for diagnosing malignant pleural mesothelioma
  • All studies pooled: 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)
  • All studies pooled: area under the summary ROC curve 0.75 (95% CI 0.72 to 0.80), which the authors described as lower than expected
  • Heterogeneity between studies: I2 was 2.97 (P=.42) for sensitivity and 89.88 (P<.001) for specificity, which the authors called massive heterogeneity in specificity
  • The cohort subgroup left out studies that used pleural fluid cytology for diagnosis; the non-cohort subgroup did not
  • Cohort study group (6 studies): AUC 0.86 (95% CI 0.83 to 0.89), sensitivity 0.68 (95% CI 0.60 to 0.75), specificity 0.91 (95% CI 0.87 to 0.94). The discussion gives the non-cohort group an AUC of 0.76 (95% CI 0.71 to 0.78).
  • Dividing studies by cutoff value (above or below 15 nM) did not reduce heterogeneity
  • Deeks' funnel plot test gave P=.13, which the authors interpreted as no publication bias
• The authors' conclusion: The authors concluded that SMRPs in pleural effusion can be a good indicator of the existence of malignant pleural mesothelioma. In their view, high levels are highly suspicious for the disease and support further invasive examination to obtain pleural biopsy results. They added that sensitivity is too low for the test to be used for screening.
• Limitations the authors state:
  • Only full English-language studies were included, and conference abstracts and non-English studies were excluded, which the authors said might cause publication bias
  • The subgroup analysis could not be done by meta-regression
  • The diagnostic accuracy of SMRPs was not assessed by disease stage
  • Several included studies had a high risk of bias in patient selection or in the reference standard (some used pleural fluid cytology for diagnosis)
  • Cutoff values differed widely between the included studies

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Soluble Mesothelin-Related Peptides (SMRP), Pleural Effusion, Pleural Mesothelioma, Meta-Analysis, Mesothelin, Tumor Marker, Malignant Mesothelioma, Odds Ratio.

Related studies

• 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)
• Diagnostic value of soluble mesothelin-related peptides for malignant mesothelioma: a meta-analysis — L. Luo, H.Z. Shi, et al. (2010)
• Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide — N. Dipalma, V. Luisi, et al. (2011)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels — E.K. Park, D. Wilson, et al. (2012)
• 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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