TY - JOUR
T1 - Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases
AU - Tsim, Selina
AU - Alexander, Laura
AU - Kelly, Caroline
AU - Shaw, Ann
AU - Hinsley, Samantha
AU - Clark, Stephen
AU - Evison, Matthew
AU - Holme, Jayne
AU - Cameron, Euan J.
AU - Sharma, Davand
AU - Wright, Angela
AU - Grundy, Seamus
AU - Grieve, Douglas
AU - Ionescu, Alina
AU - Breen, David P.
AU - Paramasivam, Elankumaran
AU - Psallidas, Ioannis
AU - Mukherjee, Dipak
AU - Chetty, Mahendran
AU - Cox, Giles
AU - Hart-Thomas, Alan
AU - Naseer, Rehan
AU - Edwards, John
AU - Daneshvar, Cyrus
AU - Panchal, Rakesh
AU - Munavvar, Mohammed
AU - Ostroff, Rachel
AU - Alexander, Leigh
AU - Hall, Holly
AU - Neilson, Matthew
AU - Miller, Crispin
AU - McCormick, Carol
AU - Thomson, Fiona
AU - Chalmers, Anthony J.
AU - Maskell, Nick A.
AU - Blyth, Kevin G.
N1 - Publisher Copyright:
© 2021 International Association for the Study of Lung Cancer
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Biomarker
KW - Fibulin-3
KW - Mesothelin
KW - Mesothelioma
KW - SOMAscan
UR - http://www.scopus.com/inward/record.url?scp=85108369006&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2021.05.018
DO - 10.1016/j.jtho.2021.05.018
M3 - Article
C2 - 34116230
AN - SCOPUS:85108369006
SN - 1556-0864
VL - 16
SP - 1705
EP - 1717
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -
