Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma

Our plain-English summary of Fibulin-3 in plasma and pleural effusion as a biomarker of mesothelioma, by K. Adamic, M.M. Malovrh, U.B. Stojkovic, et al (Radiology and Oncology, 2025).

The study

• Authors: K. Adamic, M.M. Malovrh, U.B. Stojkovic, A. Rozman
• Journal: Radiology and Oncology
• Published: 2025;59(2):225-232
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a global health concern linked to asbestos exposure. In Slovenia, regions with high asbestos exposure rates make MPM a significant public health issue. Although thoracoscopic biopsy is the gold standard for MPM diagnosis, its invasiveness highlights the need for reliable, non-invasive diagnostic biomarkers.

Patients And Methods: This prospective study evaluated the diagnostic potential of fibulin-3 as a biomarker for MPM, focusing on its ability to distinguish MPM from other pleural conditions, its association with disease stage and histological subtype, and its prognostic value for survival. Ninety patients, who underwent diagnostic thoracoscopic biopsy from January 2013 to October 2014, were included. Fibulin-3 levels in plasma and pleural effusion were measured using enzyme-linked immunosorbent assay (ELISA), and clinical data were analysed with statistical tests, including receiver operating characteristic (ROC) analysis.

Results: The study cohort comprised 32 patients with MPM, 24 with metastatic pleural carcinoma, and 34 with benign pleural diseases. Plasma fibulin-3 levels were significantly elevated (p = 0.0132) in MPM patients compared to those with benign pleural effusions due to asbestos exposure, with a cut-off of 12.31 ng/mL showing 100% specificity but low sensitivity (39.39%). Elevated fibulin-3 levels in pleural effusion correlated with advanced disease (p = 0.0463) and aggressive histological subtypes (p = 0.0324). No significant survival correlation was observed.

Conclusions: While plasma fibulin-3 is a highly specific biomarker for MPM, its low sensitivity limits its standalone diagnostic utility. Its potential role in risk stratification and early detection of MPM at-risk populations using combination of different and new biomarkers warrants further study.

© 2025 Katja Adamic et al., published by Sciendo.

In plain English

This prospective study in Golnik, Slovenia, measured a protein called fibulin-3 in blood plasma and lung-lining fluid (pleural effusion) of 90 adults having diagnostic thoracoscopy between January 2013 and October 2014. Thirty-two had malignant pleural mesothelioma, 24 cancer spread to the pleura, 13 benign asbestos-related pleural disease and 21 benign effusions from other causes. Pleural fluid was missing for 14 patients: 10 had no effusion and 4 samples were not delivered promptly. Plasma fibulin-3 was higher in the mesothelioma group (median 9.91 ng/mL) than in the benign asbestos-related group (median 7.66 ng/mL; p = 0.0132). It did not differ significantly from the other two groups. Against the 13 benign asbestos-related cases, a plasma level above 12.31 ng/mL had 100% specificity but 39.39% sensitivity for mesothelioma. Pleural fluid fibulin-3 did not differ between groups. It was higher in biphasic or sarcomatoid than in epithelioid mesothelioma, and in more advanced epithelioid disease. The article contradicts itself on any link between pleural fluid levels and survival. The authors concluded plasma fibulin-3 can help distinguish mesothelioma from benign asbestos-related conditions, but its low sensitivity limits its use alone.

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: prospective clinical study of a diagnostic biomarker (fibulin-3 measured by ELISA)
• Who was studied: 90 adults (70 male) undergoing diagnostic thoracoscopy for exudative pleural effusion at the University Clinic Golnik, Slovenia, January 2013 to October 2014. They were 32 with malignant pleural mesothelioma, 24 with metastatic pleural carcinomatosis, 13 with benign asbestos-related pleural disease and 21 with benign pleural effusions of other causes. Pleural effusion fibulin-3 could not be measured in 10 patients with no effusion (4 benign asbestos-related, 6 mesothelioma), and 4 further samples were not delivered to the laboratory promptly.
• Exposure: Fibulin-3 levels in plasma and pleural effusion were measured. Asbestos exposure was recorded by group: 13 of 13 (100.0%) in the benign asbestos-related group, 19 of 32 (59.4%) in the mesothelioma group, 2 of 24 (8.3%) in the metastatic carcinomatosis group and 4 of 21 (19.0%) in the other benign group. No fiber types, jobs or doses are given.
• Main results:
  • Plasma fibulin-3 was significantly higher in the mesothelioma group (median 9.91 ng/mL) than in the benign asbestos-related pleural disease group (median 7.66 ng/mL), p = 0.0132
  • Plasma fibulin-3 did not differ significantly between the mesothelioma group and either the metastatic carcinomatosis group or the benign non-asbestos effusion group
  • For telling mesothelioma apart from benign asbestos-related pleural disease (13 patients), plasma fibulin-3 had an area under the curve of 0.78 (p < 0.02)
  • In that same comparison (mesothelioma against benign asbestos-related pleural disease), a plasma cut-off of 12.31 ng/mL gave 100% specificity and 39.39% sensitivity
  • Pleural effusion fibulin-3 did not differ significantly between mesothelioma and benign conditions, and plasma and pleural effusion levels were not significantly correlated
  • Among the 32 mesothelioma patients (23 epithelioid, 2 sarcomatoid, 7 biphasic), pleural effusion fibulin-3 was higher in the biphasic or sarcomatoid types (median 92.3 ng/mL) than in the epithelioid type (median 66.15 ng/mL), p = 0.0324. Plasma levels did not differ by type.
  • Among epithelioid mesothelioma patients, the more advanced-stage group (G2, n = 7) had higher pleural effusion fibulin-3 than the lower-stage group (G1, n = 11), p = 0.0463
  • Median survival of mesothelioma patients was 14.1 months (interquartile range 7.7 to 26.1). Plasma fibulin-3 was not correlated with survival. The article gives conflicting statements on whether pleural effusion fibulin-3 was linked to survival.
• The authors' conclusion: The authors concluded that plasma fibulin-3 can help distinguish malignant pleural mesothelioma from benign asbestos-related pleural conditions. They also concluded that its low sensitivity, and the lack of differences from metastatic carcinomatosis and other benign pleuritis, limit its value as a standalone marker. They said larger studies are needed.
• Limitations the authors state:
  • No healthy controls and no asbestos-exposed people without pleural disease
  • Small sample size, especially for subgroup analyses
  • Lack of comprehensive asbestos exposure data

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: Fibulin-3, Pleural Effusion, Biomarker, Mesothelioma, Pleural Mesothelioma, Asbestos Exposure, Thoracoscopy, Histological Subtype.

Related studies

• Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma — H.I. Pass, S.M. Levin, et al. (2012)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis — D. Pei, Y. Li, et al. (2017)
• 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)
• Fibulin-3 as biomarker of malignant mesothelioma — C. Ledda, R. Caltabiano, et al. (2019)

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