Development of autoantibody signatures as novel diagnostic biomarkers of non-small cell lung cancer.
OBJECTIVE
To select autoantibody signatures as noninvasive biomarkers of non-small cell lung cancer (NSCLC).


METHODS
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 six-phage peptide detector was discovered by two-step immunoscreenings and was 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. The 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 six-phage peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of >92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the six phage peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the six 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 histologic types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients.


CONCLUSIONS
The six-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.
Wu
Lingling
L
Department of Epidemiology, Second Military Medical University, Shanghai, China.
Chang
Wenjun
W
Zhao
Jinfeng
J
Yu
Yongwei
Y
Tan
Xiaojie
X
Su
Tong
T
Zhao
Lijun
L
Huang
Shengdong
S
Liu
Shiyuan
S
Cao
Guangwen
G
D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000097:blood* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D016022:Case-Control Studies; D003001:Cloning, Molecular; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D010455:Peptides; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000276:immunology; D012044:Regression Analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D010455:Peptides