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 and John F R Robertson

PLOS ONE, 2012, vol. 7, issue 12, 1-9

Abstract: Background: 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. Methods and Findings: 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). Conclusion: 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.

Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0051002

DOI: 10.1371/journal.pone.0051002

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