Fibulin-3 as a biomarker for pleural mesothelioma

Our plain-English summary of Fibulin-3 as a biomarker for pleural mesothelioma, by H.I. Pass, C. Goparaju (The New England Journal of Medicine, 2013).

The study

• Authors: H.I. Pass, C. Goparaju
• Journal: The New England Journal of Medicine
• Published: 2013;368(2):190
• Type of article: Letter, Comment
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this reply, Pass and Goparaju responded to two letters, one from Hollevoet and Sharon and one from Lamote and colleagues, about their earlier report on fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. They agreed that well-designed prospective studies were needed, both for further diagnostic validation and to explore the preclinical efficacy of fibulin-3. They questioned whether soluble mesothelin-related peptides were really a "standard" biomarker for mesothelioma. They noted that their blinded validation study, which showed an area under the curve (AUC) of 0.87, was one of the only blinded validation studies in mesothelioma. They wrote that many biomarkers fail validation because of differences in patient characteristics such as glomerular filtration rate and body-mass index, poor procedures for harvesting, processing and storing samples, and inappropriate controls. They said this experience had led them to prefer plasma over serum. They reported a post hoc analysis of matched samples from their Detroit cohort: 29 patients with mesothelioma and 41 people exposed to asbestos. In this analysis the AUC was 0.74 for serum soluble mesothelin-related peptides and 1.0 for plasma fibulin-3. Citing other studies, they reported that the AUC for mesothelin-related peptides fell to 0.69 when patients with non-mesothelioma metastases were the comparison group, against 0.94 for fibulin-3. They agreed that blinded validation of other markers, alone and combined with fibulin-3, was lacking. They added that preliminary observations suggested the fibulin-3 level in pleural effusions was an independent prognostic factor.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This is not a research study but a published letter: the authors' reply to two letters about their earlier study of fibulin-3, a marker proposed for pleural mesothelioma. The authors noted that their earlier blinded validation study, which gave an area under the curve (AUC, a measure of test accuracy) of 0.87, was one of the only blinded validation studies done in mesothelioma. They reported a post hoc (after-the-fact) analysis from their Detroit cohort of 29 patients with mesotheliomas and 41 patients with exposure to asbestos. In that analysis the AUC was 0.74 for serum soluble mesothelin-related peptides and 1.0 for plasma fibulin-3. They also wrote that, in limited studies comparing serum soluble mesothelin-related peptide between patients with mesothelioma pleural effusions and patients with metastases not due to mesothelioma, the AUC for that serum marker fell to 0.69, compared with 0.94 for fibulin-3 measured in either plasma or pleural effusions. Their preliminary observations suggested that fibulin-3 in pleural effusions was an independent prognostic factor. The authors agreed that well-designed prospective 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: Letter to the editor: the original authors' reply to correspondence about their 2012 fibulin-3 study, including a post hoc analysis of their own data
• Who was studied: For the post hoc analysis: 29 patients with mesotheliomas and 41 patients with exposure to asbestos from the authors' Detroit cohort
• Exposure: Asbestos exposure in the comparison group (fiber types not stated). The markers compared were plasma fibulin-3 and serum soluble mesothelin-related peptides.
• Main results:
  • In the post hoc analysis of matched samples (29 mesothelioma patients and 41 asbestos-exposed patients), the AUC was 0.74 for serum soluble mesothelin-related peptides and 1.0 for plasma fibulin-3.
  • The authors stated that their earlier blinded validation study of fibulin-3, with an AUC of 0.87, was one of the only blinded validation studies performed in mesothelioma.
  • In limited studies cited by the authors comparing serum soluble mesothelin-related peptides between patients with mesothelioma pleural effusions and patients with metastases not due to mesothelioma, the AUC for the serum marker was 0.69, compared with 0.94 for fibulin-3, whether fibulin-3 was measured in plasma or in pleural effusions.
  • The authors' preliminary observations suggested that the fibulin-3 level in pleural effusions was an independent prognostic factor in a multivariate evaluation.
  • The authors stated that earlier experience with osteopontin led to their preference for plasma over serum samples.
• The authors' conclusion: The authors agreed with the letter writers that well-designed prospective studies are needed, and that data are lacking from blinded validation studies of other mesothelioma markers and from studies combining those markers with fibulin-3.
• Limitations the authors state:
  • The comparison of fibulin-3 with soluble mesothelin-related peptides was a post hoc analysis.
  • The prognostic finding for fibulin-3 in pleural effusions was described as preliminary.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibulin-3, Biomarker, Pleural Mesothelioma, Soluble Mesothelin-Related Peptides (SMRP), Mesothelioma, Mesothelin, Pleural Effusion.

Related studies

• 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 as a biomarker for pleural mesothelioma — K. Hollevoet, E. Sharon (2013)
• Fibulin-3 as biomarker of malignant mesothelioma — C. Ledda, R. Caltabiano, et al. (2019)
• Fibulin-3 as a biomarker for pleural mesothelioma — K. Lamote, P. Baas, et al. (2013)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)

Browse more research in The New England Journal of Medicine, or return to medical research.