Proteomics as a Method for Early Detection of Cancer: A Review of Proteomics, Exhaled Breath Condensate, and Lung Cancer Screening

The study of expressed proteins in neoplasia is undergoing a revolution with the advent of proteomic analysis. Unlike genomic studies where individual changes may have no functional significance, protein expression is closely aligned with cellular activity. This perspective will review proteomics as a method of detecting markers of neoplasia with a particular emphasis on lung cancer and the potential to sample the lung by exhaled breath condensate (EBC). EBC collection is a simple, new, and noninvasive technique, which allows sampling of lower respiratory tract fluid. EBC enables the study of a wide variety of biological markers from low molecular weight mediators to macromolecules, such as proteins, in a range of pulmonary diseases. EBC may be applied to the detection of lung cancer where it could be a tool in early diagnosis. This perspective will explore the potential of applying proteomics to the EBC from lung cancer patients as an example of detecting potential biomarkers of disease and progression

Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals

<p>To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals.</p><p>Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm(3)), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference.</p><p>Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days.</p><p>All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT a parts per thousand currency sign232 days. Lowering the VDT cutoff may reduce false-positive referrals.</p><p>aEuro cent Lung nodules are common in CT lung cancer screening, most being benign</p><p>aEuro cent Short-term follow-up CT can identify fast-growing intermediate-size lung nodules</p><p>aEuro cent Most fast-growing nodules on short-term follow-up CT still prove to be benign</p><p>aEuro cent A new volume-doubling time (VDT) cut-off is proposed for lung screening</p><p>aEuro cent The optimised VDT cutoff may decrease false-positive case referrals for lung cancer.</p>