Profiling tumor-associated antibodies for early detection of non-small cell lung cancer.
BACKGROUND
A blood test for non-small cell lung cancer (NSCLC) may be a valuable tool for use in a comprehensive lung cancer screening strategy. Here we report the potential of autoantibody profiling to detect early-stage and occult NSCLC.


METHODS
T7-phage NSCLC cDNA libraries were screened with patient plasma to identify phage-expressed proteins recognized by tumor-associated antibodies. Two hundred twelve immunogenic phage-expressed proteins, identified from 4000 clones, were statistically ranked for their individual reactivity with 23 stage I cancer patient and 23 risk-matched control samples. All 46 samples were used as a training set to define a combination of markers that were best able to distinguish patient from control samples; this set of classifiers was then examined using leave-one-out cross-validation. Markers were then used to predict probability of disease in 102 samples from the Mayo Clinic CT Screening Trial (six prevalence cancer samples, 40 drawn 1 to 5 years before diagnosis, and 56 risk-matched controls).


RESULTS
Measurements of the five most predictive antibody markers in 46 cases and controls were combined in a logistic regression model that yielded area under the receiver operating characteristics curve of 0.99; leave-one-out validation achieved 91.3% sensitivity and 91.3% specificity. In testing this marker set with samples from the Mayo Clinic Lung Screening Trial, we correctly predicted six of six prevalence cancers, 32 of 40 cancers from samples drawn 1 to 5 years before radiographic detection on incidence screening, and 49 of 56 risk-matched controls.


CONCLUSIONS
Antibody profiling may be a useful tool for early detection of NSCLC.
Zhong
Li
L
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Kentucky, Lexington, KY 40536, USA. lzhon2@uky.edu
Coe
Sarah P
SP
Stromberg
Arnold J
AJ
Khattar
Nada H
NH
Jett
James R
JR
Hirschowitz
Edward A
EA
D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology*; D017123:Bacteriophage T7 / Q000235:genetics; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology* / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D015723:Gene Library; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor