Fibulin-3 as biomarker of malignant mesothelioma

Our plain-English summary of Fibulin-3 as biomarker of malignant mesothelioma, by C. Ledda, R. Caltabiano, F. Vella, et al (Biomarkers in Medicine, 2019).

The study

• Authors: C. Ledda, R. Caltabiano, F. Vella, S. Matera, A. Marconi, C. Loreto, V. Rapisarda
• Journal: Biomarkers in Medicine
• Published: 2019;13(10):875-886
• Type of article: Systematic review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Many malignant diseases are associated with past asbestos exposure; the most lethal and strictly related to previous fiber exposure being malignant mesothelioma (MM). Effective preventive protocols may include sensitive and specific biomarkers. The role of Fb-3 has been recently investigated for MM early detection, but its role is still under debate. After an independent search for scientific literature, nine studies were included for a systematic review. Human Fb-3 levels seem to be able to separate healthy people with previous exposure to asbestiform fibers from MM patients. Fb-3 blood levels can distinguish MM effusions from other malignant and benign effusions. Furthers investigations on more significant groups of patients are desirable to validate and assess the validity of combining Fb-3 with other biomarkers.

In plain English

This article was a systematic review, not a new study. The authors searched the SCOPUS and Medline databases for research available up to 5 May 2018 on fibulin-3 (Fb-3), a protein studied as a possible blood or pleural-fluid marker of malignant mesothelioma (MM) after exposure to asbestos or asbestos-like fibers. Of 22 documents found, nine studies from the USA, Italy, Australia, Egypt and Turkey were included. Their results were described study by study and not pooled. The reviewed studies reported differing results. In one study (Pass et al.), a plasma cut point of 52 ng/ml gave 97% sensitivity at 95% specificity, but sensitivity was below 40% in a blinded external validation set. Another study (Creaney et al.) reported 22% sensitivity at 95% specificity at the same cut point and found mesothelin more accurate. A study of workers exposed to the fiber fluoro-edenite found higher median plasma Fb-3 than in unexposed controls. The authors concluded that Fb-3 levels seem able to separate healthy asbestos-exposed people from MM patients. They noted small patient numbers and weak cut-off values, and called for larger studies.

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 of published studies, reported using the PRISMA statement; no pooled analysis
• Who was studied: Nine studies (published 2012 to 2016, from the USA, Italy, Australia, Egypt and Turkey) found in SCOPUS and Medline searches covering research available until 5 May 2018. Of 22 documents retrieved, 12 were excluded on title and abstract and 1 after full-text review.
• Exposure: Fb-3 measured in plasma, serum, pleural fluid or tumor tissue in people with occupational or environmental exposure to asbestos or asbestiform fibers, including fluoro-edenite
• Main results:
  • Pass et al. (MM cases compared with all other patients): a plasma Fb-3 cut point of 52 ng/ml gave 97% sensitivity at 95% specificity
  • Pass et al., blinded external validation set: sensitivity was below 40% at 95% specificity, with an AUC of 0.87
  • Creaney et al. (153 patients, 82 with MM): plasma Fb-3 had 22% sensitivity at 95% specificity at the 52 ng/ml cut point, with an AUC of 0.671 (0.606 to 0.732), lower than mesothelin
  • Creaney et al., pleural effusion: Fb-3 had 59% sensitivity and 52% specificity at a threshold of 346 ng/ml
  • Agha et al. (45 patients with exudative pleural effusion): a pleural fluid Fb-3 cut-off of 150 ng/ml distinguished MM from metastatic carcinoma with an AUC of 0.878, sensitivity 72.3% and specificity 80%
  • Kaya et al. (43 MM patients and 40 controls): mean serum Fb-3 was 90.3 (standard deviation 42.1) ng/ml in MM patients and 17.8 (standard deviation 12.7) ng/ml in controls. The best cut-off, 36.6 ng/ml, gave 93% sensitivity and 90% specificity.
  • Corradi et al.: serum Fb-3 was higher in MM than in non-small-cell lung cancer and control groups, but not significantly different from the asbestosis group
  • Rapisarda et al. (2015), workers exposed to fluoro-edenite compared with nonexposed controls: median plasma Fb-3 was 12.96 ng/ml in exposed workers and 5.29 ng/ml in controls. Pleural plaques were found in 52% of exposed subjects and in none of the controls.
• The authors' conclusion: The authors concluded that Fb-3 levels seem able to separate healthy people with asbestos exposure from MM patients, and that Fb-3 blood levels can differentiate MM effusions from other malignant and benign effusions. They called for larger studies to validate these results and to assess combining Fb-3 with other biomarkers.
• Limitations the authors state:
  • The authors stated that the main limitation of the reviewed studies was the low number of patients
  • The authors stated that the cut-off values are still weak
  • The authors stated that pleural fluid samples are not practical for monitoring populations in clinical practice

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, Biomarker, Malignant Mesothelioma, Asbestos Exposure, Systematic Review, Asbestiform.

Related studies

• Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report — R. Caltabiano, C. Loreto, et al. (2018)
• Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma — H.I. Pass, S.M. Levin, et al. (2012)
• Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population — Z. Jiang, S. Ying, et al. (2017)
• Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis — M.B. Kirschner, E. Pulford, et al. (2015)
• 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)
• FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study — V. Rapisarda, C. Ledda, et al. (2015)

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