Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.

<h4>Background</h4>The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to a...

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Autores principales:	Isabel K Macdonald, Andrea Murray, Graham F Healey, Celine B Parsy-Kowalska, Jared Allen, Jane McElveen, Chris Robertson, Herbert F Sewell, Caroline J Chapman, John F R Robertson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8438960788f54e9abee9c438965f1446
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spelling	oai:doaj.org-article:8438960788f54e9abee9c438965f14462021-11-18T08:05:13ZApplication of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.1932-620310.1371/journal.pone.0051002https://doaj.org/article/8438960788f54e9abee9c438965f14462012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23272083/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)).<h4>Methods and findings</h4>Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7).<h4>Conclusion</h4>This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT--Lung test, and so further aid the early detection of lung cancer.Isabel K MacdonaldAndrea MurrayGraham F HealeyCeline B Parsy-KowalskaJared AllenJane McElveenChris RobertsonHerbert F SewellCaroline J ChapmanJohn F R RobertsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51002 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabel K Macdonald Andrea Murray Graham F Healey Celine B Parsy-Kowalska Jared Allen Jane McElveen Chris Robertson Herbert F Sewell Caroline J Chapman John F R Robertson Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
description	<h4>Background</h4>The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)).<h4>Methods and findings</h4>Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7).<h4>Conclusion</h4>This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT--Lung test, and so further aid the early detection of lung cancer.
format	article
author	Isabel K Macdonald Andrea Murray Graham F Healey Celine B Parsy-Kowalska Jared Allen Jane McElveen Chris Robertson Herbert F Sewell Caroline J Chapman John F R Robertson
author_facet	Isabel K Macdonald Andrea Murray Graham F Healey Celine B Parsy-Kowalska Jared Allen Jane McElveen Chris Robertson Herbert F Sewell Caroline J Chapman John F R Robertson
author_sort	Isabel K Macdonald
title	Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
title_short	Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
title_full	Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
title_fullStr	Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
title_full_unstemmed	Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.
title_sort	application of a high throughput method of biomarker discovery to improvement of the earlycdt(®)-lung test.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8438960788f54e9abee9c438965f1446
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Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®)-Lung Test.

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