Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases

Selina Tsim; Laura Alexander; Caroline Kelly; Ann Shaw; Samantha Hinsley; Stephen Clark; Matthew Evison; Jayne Holme; Euan J. Cameron; Davand Sharma; Angela Wright; Seamus Grundy; Douglas Grieve; Alina Ionescu; David P. Breen; Elankumaran Paramasivam; Ioannis Psallidas; Dipak Mukherjee; Mahendran Chetty; Giles Cox; Alan Hart-Thomas; Rehan Naseer; John Edwards; Cyrus Daneshvar; Rakesh Panchal; Mohammed Munavvar; Rachel Ostroff; Leigh Alexander; Holly Hall; Matthew Neilson; Crispin Miller; Carol McCormick; Fiona Thomson; Anthony J. Chalmers; Nick A. Maskell; Kevin G. Blyth

doi:10.1016/j.jtho.2021.05.018

Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases

Selina Tsim
, Laura Alexander
, Caroline Kelly
, Ann Shaw
, Samantha Hinsley
, Stephen Clark
, Matthew Evison
, Jayne Holme
, Euan J. Cameron
, Davand Sharma
, Angela Wright
, Seamus Grundy
, Douglas Grieve
, Alina Ionescu
, David P. Breen
, Elankumaran Paramasivam
, Ioannis Psallidas
, Dipak Mukherjee
, Mahendran Chetty
, Giles Cox

Alan Hart-Thomas, Rehan Naseer, John Edwards, Cyrus Daneshvar, Rakesh Panchal, Mohammed Munavvar, Rachel Ostroff, Leigh Alexander, Holly Hall, Matthew Neilson, Crispin Miller, Carol McCormick, Fiona Thomson, Anthony J. Chalmers, Nick A. Maskell, Kevin G. Blyth^*

^*Corresponding author for this work

Queen Elizabeth University Hospital, Glasgow
University of Glasgow
Manchester University NHS Foundation Trust
NHS Forth Valley
NHS Greater Glasgow and Clyde
Glasgow Royal Infirmary
Salford Royal Hospital
Aneurin Bevan Health Board
University of Galway
Leeds Teaching Hospitals NHS Trust
Oxford University Hospitals NHS Foundation Trust
Mid and South Essex NHS Foundation Trust
NHS Grampian
Sherwood Forest Hospitals NHS Foundation Trust
Calderdale and Huddersfield NHS Foundation Trust
Northern General Hospital
University Hospitals Plymouth NHS Trust
Glenfield Hospital
Lancashire Teaching Hospitals NHS Foundation Trust
SomaLogic
Beatson Institute for Cancer Research
University of Bristol

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1705-1717
Number of pages	13
Journal	Journal of Thoracic Oncology
Volume	16
Issue number	10
DOIs	https://doi.org/10.1016/j.jtho.2021.05.018
Publication status	Published - Oct 2021
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine

Keywords

Biomarker
Fibulin-3
Mesothelin
Mesothelioma
SOMAscan

Access to Document

10.1016/j.jtho.2021.05.018

Cite this

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, E., Psallidas, I., Mukherjee, D., Chetty, M., ... Blyth, K. G. (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), 1705-1717. https://doi.org/10.1016/j.jtho.2021.05.018

@article{145ec5a4589b4aee8b6ed56b21f6f585,

title = "Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases",

abstract = "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.",

keywords = "Biomarker, Fibulin-3, Mesothelin, Mesothelioma, SOMAscan",

author = "Selina Tsim and Laura Alexander and Caroline Kelly and Ann Shaw and Samantha Hinsley and Stephen Clark and Matthew Evison and Jayne Holme and Cameron, \{Euan J.\} and Davand Sharma and Angela Wright and Seamus Grundy and Douglas Grieve and Alina Ionescu and Breen, \{David P.\} and Elankumaran Paramasivam and Ioannis Psallidas and Dipak Mukherjee and Mahendran Chetty and Giles Cox and Alan Hart-Thomas and Rehan Naseer and John Edwards and Cyrus Daneshvar and Rakesh Panchal and Mohammed Munavvar and Rachel Ostroff and Leigh Alexander and Holly Hall and Matthew Neilson and Crispin Miller and Carol McCormick and Fiona Thomson and Chalmers, \{Anthony J.\} and Maskell, \{Nick A.\} and Blyth, \{Kevin G.\}",

note = "Publisher Copyright: {\textcopyright} 2021 International Association for the Study of Lung Cancer",

year = "2021",

month = oct,

doi = "10.1016/j.jtho.2021.05.018",

language = "English",

volume = "16",

pages = "1705--1717",

journal = "Journal of Thoracic Oncology",

issn = "1556-0864",

publisher = "Elsevier Inc.",

number = "10",

}

Tsim, S, Alexander, L, Kelly, C, Shaw, A, Hinsley, S, Clark, S, Evison, M, Holme, J, Cameron, EJ, Sharma, D, Wright, A, Grundy, S, Grieve, D, Ionescu, A, Breen, DP, Paramasivam, 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, Chalmers, AJ, Maskell, NA & Blyth, KG 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, vol. 16, no. 10, pp. 1705-1717. https://doi.org/10.1016/j.jtho.2021.05.018

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.

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 - https://www.scopus.com/pages/publications/85108369006

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 -

Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases

Abstract

UN SDGs

ASJC Scopus subject areas

Keywords

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