Abstract
BackgroundCancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response.MethodsEighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance.ResultsSeven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified.ConclusionOur results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer.
Highlights
Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer
Eighty arrays with 24 sera from lung cancer patients, 24 normal sera, or 32 sera from patients with chronic obstructive pulmonary disease (COPD) were analyzed
While lung cancer patients were largely separated from the other two groups of patients, there was no clear separation between COPD and normal
Summary
Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. Direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. As treatment is efficacious only for those patients who are diagnosed sufficiently early in the disease process, a significant reduction in patient mortality may result from earlier detection of lung cancer, including combinations of biomarkers with spiral CT imaging [2]. Direct serum protein profiling by matrix assisted laser desorption ionization (MALDI) mass spectrometry [4,5] has uncovered distinct mass profiles in several common types of cancer. Given the limited dynamic range of MALDI, it is likely that distinctive features observed in serum with this approach represent relatively abundant proteins
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