Serum proteomics and plasma fibulin-3 in differentiation of mesothelioma from asbestos-exposed controls and patients with other pleural diseases

Tsim, S. et al. (2021) Serum proteomics and plasma fibulin-3 in differentiation of mesothelioma from asbestos-exposed controls and patients with other pleural diseases. Journal of Thoracic Oncology, 16(10), pp. 1705-1717. (doi: 10.1016/j.jtho.2021.05.018) (PMID:34116230) (PMCID:PMC8514249)

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Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Item Type:Articles
Additional Information:The study was funded by the Chief Scientist Office (Scottish Government, reference ETM/285). SomaLogic Inc. funded the proteomic analyses. The Glasgow Experimental Cancer Medicine Centre (through Cancer Research UK) funded biomarker and data analyses. Cancer Research UK Core funding to the Beatson Institute (reference A17196, A31287) and Prof. Miller (reference A29801) supported bioinformatic analyses.
Glasgow Author(s) Enlighten ID:Alexander, Mrs Laura and Miller, Professor Crispin and Kelly, Mrs Caroline and Thomson, Dr Fiona and Hinsley, Miss Samantha and Blyth, Professor Kevin and Neilson, Dr Matthew and Cameron, Dr Euan and McCormick, Mrs Carol and Shaw, Ms Ann and Tsim, Dr Selina and Clark, Mr Stephen and Chalmers, Professor Anthony
Authors: Tsim, S., Alexander, L., Kelly, C., Shaw, A., Hinsley, S., Clark, S., Evison, M., Holme, J., Cameron, E. J., Sharma, D., Wright, A., Grundy, S., Grieve, D., Ionescu, A., Breen, D. P., Paramasivam, MD, E., Psallidas, I., Mukherjee, D., Chetty, M., Cox, G., Hart-Thomas, A., Naseer, R., Edwards, J., Daneshvar, C., Panchal, R., Munavvar, M., Ostroff, R., Alexander, L., Hall, H., Neilson, M., Miller, C., McCormick, C., Thomson, F. T., Chalmers, A. J., Maskell, N. A., and Blyth, K. G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Thoracic Oncology
ISSN (Online):1556-1380
Published Online:08 June 2021
Copyright Holders:Copyright © 2021 International Association for the Study of Lung Cancer
First Published:First published in Journal of Thoracic Oncology 16(10): 1705-1717
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
168769An examination of diagnostic and prognostic biomarkers in malignant pleural mesotheliomaKevin BlythOffice of the Chief Scientific Adviser (CSO)ETM/285CS - Clinical Research Garscube