Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases.
Biomarker
Fibulin-3
Mesothelin
Mesothelioma
SOMAscan
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
19
01
2021
revised:
20
04
2021
accepted:
09
05
2021
pubmed:
12
6
2021
medline:
28
10
2021
entrez:
11
6
2021
Statut:
ppublish
Résumé
Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory. A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure. A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557-0.664], p = 0.0015) and 0.516 [0.443-0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume. SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.
Identifiants
pubmed: 34116230
pii: S1556-0864(21)02189-4
doi: 10.1016/j.jtho.2021.05.018
pmc: PMC8514249
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Calcium-Binding Proteins
0
EFEMP1 protein, human
0
Extracellular Matrix Proteins
0
GPI-Linked Proteins
0
fibulin
0
Asbestos
1332-21-4
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1705-1717Subventions
Organisme : Cancer Research UK
ID : A17196
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A31287
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A29801
Pays : United Kingdom
Informations de copyright
Copyright © 2021 International Association for the Study of Lung Cancer. All rights reserved.
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