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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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)).

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).

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.
LanguageEnglish
Article numbere51002
Number of pages10
JournalPLOS One
Volume7
Issue number12
DOIs
Publication statusPublished - 13 Dec 2012

Fingerprint

Biomarkers
biomarkers
lungs
Throughput
lung neoplasms
Lung
autoantibodies
Autoantibodies
Lung Neoplasms
Screening
Proteins
testing
screening
Assays
Early Detection of Cancer
proteins
methodology
Cloning
Technology
Sensitivity and Specificity

Keywords

  • EarlyCDT®-Lung Test
  • lung cancer
  • cancer detection

Cite this

Macdonald, I. K., Murray, A., Healey, G. F., Parsy-Kowalska, C. B., Allen, J., McElveen, J., ... Robertson, J. F. R. (2012). Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT®-Lung Test. PLOS One, 7(12), [e51002]. https://doi.org/10.1371/journal.pone.0051002
Macdonald, Isabel K. ; Murray, Andrea ; Healey, Graham F. ; Parsy-Kowalska, Celine B. ; Allen, Jared ; McElveen, Jane ; Robertson, Chris ; Sewell, Herbert F. ; Chapman, Caroline J. ; Robertson, John F.R. / Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT®-Lung Test. In: PLOS One. 2012 ; Vol. 7, No. 12.
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Macdonald, IK, Murray, A, Healey, GF, Parsy-Kowalska, CB, Allen, J, McElveen, J, Robertson, C, Sewell, HF, Chapman, CJ & Robertson, JFR 2012, 'Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT®-Lung Test' PLOS One, vol. 7, no. 12, e51002. https://doi.org/10.1371/journal.pone.0051002

Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT®-Lung Test. / Macdonald, Isabel K.; Murray, Andrea; Healey, Graham F.; Parsy-Kowalska, Celine B.; Allen, Jared; McElveen, Jane; Robertson, Chris; Sewell, Herbert F.; Chapman, Caroline J.; Robertson, John F.R.

In: PLOS One, Vol. 7, No. 12, e51002, 13.12.2012.

Research output: Contribution to journalArticle

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AU - Robertson, Chris

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Macdonald IK, Murray A, Healey GF, Parsy-Kowalska CB, Allen J, McElveen J et al. Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT®-Lung Test. PLOS One. 2012 Dec 13;7(12). e51002. https://doi.org/10.1371/journal.pone.0051002