PURPOSE: To select autoantibody signatures as noninvasive biomarkers of non-small cell lung cancer (NSCLC).EXPERIMENTAL DESIGN: A phage cDNA expression library was constructed with fresh samples from 30 lung cancer patients and biopanned using serum pools of 10 NSCLC patients and 10 healthy controls. A 6-phage-peptide detector was discovered by two-step immunoscreenings, and validated in an independent set of 90 NSCLC patients and 90 matched healthy controls, 30 NSCLC patients with chemotherapy, and 12 chronic obstructive pulmonary disease (COPD) patients. Expression of a peptide target was validated by using immunohistochemistry. Factors affecting NSCLC-related death were evaluated by Cox regression analysis. RESULTS: Six phage-peptide clones showing higher seroreactivity than others in 30 NSCLC patients were selected for diagnostic validation. The 6-phage-peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of greater than 92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the 6 phage-peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the 6 phage-peptides, one encoded a peptide showing 100% homology to olfactomedin 1. Expression of olfactomedin 1 protein was significantly higher in lung adenocarcinoma than in lung cancer of other histological types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients. CONCLUSIONS: The 6-phage-peptide-detector stands out as promising diagnostic biomarkers for NSCLC, unlikely for NSCLC relapse after chemotherapy. Olfactomedin 1 may be a novel target of lung adenocarcinoma.
详细资料
文献种类: Journal Article
期刊名称: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
期刊缩写: Clin Cancer Res
期卷页: 2010年
地址: Epidemiology, Second Military Medical University