Abstract
BackgroundSera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.MethodsWe performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.ResultsStatistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.ConclusionA pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.
Highlights
Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways
CT scans of the chest have greater sensitivity compared to posterior-anterior chest x-rays in detecting small non-calcified nodules that may represent early lung cancers; this technique has poor specificity because of the high prevalence of non-calcified and ground glass pulmonary nodules [2,3]. These nodules may be due to granulomatous disease, fibrosis, atypical adenomatous hyperplasia (AAH), bronchoalveolar carcinoma (BAC), adenocarcinoma, or slowly resolving inflammatory lesions
Using a mini-array of TAAs, we previously showed a greatly increased frequency of positive immune reactivity in breast, lung, prostate, gastric, colorectal and hepatocellular carcinoma [23,24,25,26]
Summary
Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways. CT scans of the chest have greater sensitivity compared to posterior-anterior chest x-rays in detecting small non-calcified nodules that may represent early lung cancers; this technique has poor specificity because of the high prevalence of non-calcified and ground glass pulmonary nodules [2,3]. These nodules may be due to granulomatous disease, fibrosis, atypical adenomatous hyperplasia (AAH), bronchoalveolar carcinoma (BAC), adenocarcinoma, or slowly resolving inflammatory lesions. In 133 lung cancer patients, antibodies to p53 were detected in 25 (18.8%), with significant associations with squamous cell
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