Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis

Our plain-English summary of Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis, by D. Pei, Y. Li, X. Liu, et al (Oncotarget, 2017).

The study

• Authors: D. Pei, Y. Li, X. Liu, S. Yan, X. Guo, X. Xu, X. Guo
• Journal: Oncotarget
• Published: 2017;8(8):13030-13038
• Type of article: Meta-analysis
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Fibulin-3 has emerged as a promising novel biomarker in conforming or monitoring malignant pleural mesothelioma (MPM). This study sought to evaluate the diagnostic and prognostic efficacies of humoral fibulin-3 for MPM. Seven eligible publications comprising 468 MPM cases for diagnosis, and 138 for prognosis were identified. Results manifested that humoral fibulin-3 sustained a pooled sensitivity of 0.62 (95% CI: 0.45-0.77) and specificity of 0.82 (95% CI: 0.73-0.89) in discriminating MPM patients from cancer-free individuals, corresponding to an AUC (area under the curve) of 0.81. For the survival analysis, fibulin-3 expression was not markedly associated with overall survival (OS) time of the MPM patients [HR (hazard ratio): 1.84, 95% CI: 0.75-4.56, P = 0.185]. In the subgroup analyses stratified by test matrix and ethnicity, data revealed that serum-based fibulin-3 examination achieved superior accuracy than plasma-based analysis (sensitivity: 0.77 versus 0.54; specificity: 0.85 versus 0.77; AUC: 0.92 versus 0.69); additionally, testing of fibulin-3 in Europeans retained higher efficacy than those in Americans and Australians. Taken together, fibulin-3 confers a relatively high diagnostic efficacy and is acceptable to be an auxiliary biomarker to aid in MPM identification.

In plain English

This was a meta-analysis pooling results from earlier published studies. It asked whether levels of a protein called fibulin-3, measured in blood or pleural fluid, can help diagnose malignant pleural mesothelioma (MPM) or predict survival. The authors searched PubMed up to June 30, 2016. They included six studies on diagnosis (468 MPM patients and 664 controls) and three on survival (138 MPM cases). Controls included healthy people, asbestos-exposed individuals and people with fluid around the lungs not caused by MPM. After two outlier studies were removed, fibulin-3 had a pooled sensitivity of 0.62 (95% CI 0.45 to 0.77) and specificity of 0.82 (95% CI 0.73 to 0.89), with an area under the curve of 0.81. Fibulin-3 level was not significantly associated with overall survival (hazard ratio 1.84, 95% CI 0.75 to 4.56, P = 0.185). Serum tests performed better than plasma tests. Studies the authors grouped as European performed better than American or Australian ones. Results varied widely between studies. The authors concluded that fibulin-3 is acceptable as a diagnostic biomarker for MPM. They noted limitations including population bias, mixed control groups and small numbers in subgroups.

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: Meta-analysis of published studies on the diagnostic and prognostic accuracy of humoral (blood or effusion) fibulin-3 for malignant pleural mesothelioma, following PRISMA
• Who was studied: Six diagnostic studies (468 MPM patients and 664 matched controls) and three prognostic studies (138 MPM cases), found by searching PubMed up to June 30, 2016. Study populations were Australians, Americans and Europeans. The article's study table lists the non-American, non-Australian studies as from Turkey.
• Exposure: Not an asbestos exposure study. The item measured was fibulin-3 levels in plasma, serum and pleural effusion, tested by ELISA. Controls included healthy participants, asbestos-exposed individuals and non-MPM related effusions. No fiber types are specified.
• Main results:
  • Overall, after two outlier studies were removed, fibulin-3 distinguished MPM patients from cancer-free participants with a pooled sensitivity of 0.62 (95% CI 0.45 to 0.77), specificity of 0.82 (95% CI 0.73 to 0.89) and AUC of 0.81
  • Two individual studies were judged to be outliers and were removed from the adjusted analysis
  • The pooled diagnostic odds ratio for the adjusted overall analysis was 7.44
  • Assuming a pre-test probability of 20%, a positive fibulin-3 test raised the probability of MPM to 46% and a negative test lowered it to 10%
  • In the three prognostic studies, fibulin-3 level was not significantly associated with overall survival in MPM patients (HR 1.84, 95% CI 0.75 to 4.56, P = 0.185)
  • Serum-based testing was more accurate than plasma-based testing (sensitivity 0.77 vs 0.54; specificity 0.85 vs 0.77; DOR 29.11 vs 3.55; AUC 0.92 vs 0.69)
  • Fibulin-3 testing in the European subgroup performed better than in the American and Australian subgroups
  • There was significant heterogeneity between studies, so a random effect model was used. In meta-regression, test matrix and control size were the likely main sources of this heterogeneity.
  • No significant publication bias was found
• The authors' conclusion: The authors concluded that humoral fibulin-3 is acceptable as a diagnostic biomarker for MPM. They added that further studies are needed on its prognostic role.
• Limitations the authors state:
  • Population bias, complicated control sources and small case numbers in the stratified analyses
  • The prognostic result may not reflect fibulin-3's true prognostic value, because of significant heterogeneity, limited sample size and few studies
  • Each ethnicity subgroup analysis included only 2 studies and showed high heterogeneity
  • Control sources were mixed, and concomitant disease conditions among patients were unclear

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, Meta-Analysis, Biomarker, Prognosis, Overall Survival, Hazard Ratio.

Related studies

• Diagnostic value of fibulin-3 for malignant pleural mesothelioma: A systematic review and meta-analysis — R. Ren, P. Yin, et al. (2016)
• Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma — K. Adamic, M.M. Malovrh, et al. (2025)
• 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)
• Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study — S. Tsim, C. Kelly, et al. (2016)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)

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