Diagnostic value of fibulin-3 for malignant pleural mesothelioma: A systematic review and meta-analysis

Our plain-English summary of Diagnostic value of fibulin-3 for malignant pleural mesothelioma: A systematic review and meta-analysis, by R. Ren, P. Yin, Y. Zhang, et al (Oncotarget, 2016).

The study

• Authors: R. Ren, P. Yin, Y. Zhang, J. Zhou, Y. Zhou, R. Xu, H. Lin, C. Huang
• Journal: Oncotarget
• Published: 2016;7(51):84851-84859
• Type of article: Meta-analysis, Systematic review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Several studies have investigated the diagnostic value of fibulin-3 for malignant pleural mesothelioma (MPM), but the results were various. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic value of fibulin-3 for MPM.

Results: Eight studies were included in this work. The overall sensitivity of blood fibulin-3 were 0.87 (95% CI, 0.58 - 0.97) and 0.89 (95% CI, 0.77 - 0.95), respectively. The overall sensitivity and specificity of PF fibulin-3 for MPM were 0.73 (95% CI, 0.54 - 0.86) and 0.80 (95% CI, 0.60 - 0.91), respectively. The area under curve of blood and pleural effusion (PF) Fibulin-3 were 0.94 (95% CI, 0.91 - 0.96) 0.83 (95% CI, 0.79 - 0.86), respectively.

Methods: PubMed and EMBASE databases were searched up to July 29, 2016 to verify studies investigating the diagnostic value of fibulin-3 for MPM. The quality of eligible studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2). The overall sensitivity and specificity were pooled using a bivariate model.

Conclusion: Fibuoin-3 is a useful diagnostic marker for MPM.

In plain English

This was a systematic review and meta-analysis that pooled eight published studies measuring a protein called fibulin-3 to diagnose malignant pleural mesothelioma (MPM). The studies had between 36 and 228 participants. Their comparison groups varied and included asbestos-exposed persons, patients with pleural effusion (fluid around the lung), patients with metastatic pleural malignancy and healthy controls. For fibulin-3 in blood, pooled sensitivity (the share of MPM patients correctly detected) was 0.87 (95% confidence interval 0.58 to 0.97). Pooled specificity (the share without MPM correctly ruled out) was 0.89 (0.77 to 0.95). For fibulin-3 in pleural effusion, sensitivity was 0.73 (0.54 to 0.86) and specificity was 0.80 (0.60 to 0.91). Results varied a lot between studies for both tests; for the blood test, the study features the authors examined did not explain this. All studies were rated at high risk of bias in how participants were selected. The authors concluded that fibulin-3 was a useful diagnostic marker for MPM. Because there were few studies and this selection risk, they said further well-designed studies are needed.

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 eight published diagnostic accuracy studies
• Who was studied: Eight published studies; one study (Pass) contributed two cohorts. Sample sizes ranged from 36 to 228. Comparison groups included asbestos-exposed persons, patients with pleural effusion, patients with metastatic pleural malignancy, healthy controls and surgical patients. Studies came from the USA, Australia, Switzerland, Egypt, Turkey, and the USA and UK; they were published 2012 to 2016.
• Exposure: Not an asbestos exposure study. The test studied was fibulin-3 measured in blood (serum or plasma) or in pleural effusion, all by ELISA. Asbestos-exposed persons appeared only as comparison groups in some studies.
• Main results:
  • Blood fibulin-3, pooled across studies: sensitivity 0.87 (95% CI, 0.58 to 0.97) and specificity 0.89 (95% CI, 0.77 to 0.95) for MPM.
  • Pleural effusion fibulin-3, pooled: sensitivity 0.73 (95% CI, 0.54 to 0.86) and specificity 0.80 (95% CI, 0.60 to 0.91) for MPM.
  • Area under the summary ROC curve was 0.94 (95% CI, 0.91 to 0.96) for blood fibulin-3 and 0.83 (95% CI, 0.79 to 0.86) for pleural effusion fibulin-3.
  • Diagnostic odds ratios were 53 (95% CI, 10 to 289) for blood fibulin-3 and 11 (95% CI, 2 to 59) for pleural effusion fibulin-3.
  • For blood fibulin-3 there was significant heterogeneity between studies: I2 of 96 for sensitivity and 93 for specificity.
  • In subgroup analysis of blood fibulin-3 only, study design (prospective or other), sample type (serum or plasma) and control group (asbestos-exposed only or others) did not explain the heterogeneity.
  • For pleural effusion fibulin-3, heterogeneity was also large: I2 of 91 for sensitivity and 92 for specificity.
  • The funnel plot did not indicate significant publication bias (P = 0.70).
• The authors' conclusion: The authors concluded that fibulin-3 was a useful diagnostic marker for MPM. They added that further well-designed studies are needed to rigorously evaluate its diagnostic value.
• Limitations the authors state:
  • The number of eligible studies was small, and all had a higher risk of bias in subject selection.
  • The included studies mainly used a two-gate design, which can cause participant selection bias.
  • Participants in the included studies may not represent the people in whom MPM is actually suspected.
  • In all but one study, it was not reported whether the fibulin-3 test was performed blind.
  • The sources of heterogeneity remain unexplained; more studies are needed to explore them.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibulin-3, Pleural Mesothelioma, Systematic Review, Meta-Analysis, Pleural Effusion.

Related studies

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• Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China — Z. Jiang, W. Shen, et al. (2020)
• Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma — K. Adamic, M.M. Malovrh, et al. (2025)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• Fibulin-3 as biomarker of malignant mesothelioma — C. Ledda, R. Caltabiano, et al. (2019)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)

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