Key Point

Antibody profiling is a promising technique for early diagnosis of non–small cell lung cancer.

LEXINGTON, KY, AND ROCHESTER, MINN—Antibody profiling appears to be a promising technique for diagnosing non–small cell lung cancer (NSCLC). Li Zhong, PhD, Assistant Professor of Medicine at the University of Kentucky College of Medicine, and his colleagues identified five NSCLC-associated proteins that have the ability to distinguish patient plasma samples from risk-matched control plasma samples.¹

To narrow the number of potential markers for the diagnosis of NSCLC, the researchers "biopan-enriched the immunogenic phage content of two NSCLC T7 libraries, used fluorescent protein microarrays to screen 4,000 clones, and subsequently refined a list of potential markers to generate a diagnostic array capable of distinguishing patients with NSCLC from normal control subjects."

Dr. Zhong and his colleagues combined five of the most predictive phage-expressed proteins onto a single protein "diagnostic chip" and evaluated its ability to predict disease in patient samples.

ACCURACY OF THE ASSAY

Measurements of the five most predictive phage proteins were combined in a logistic regression model that achieved 90% sensitivity and 95% specificity in prediction of patient samples. Using the leave-one-out validation method, the researchers were able to obtain a diagnostic accuracy of 88.9% within 81 NSCLC and risk-matched control samples. They tested predominantly patients with advanced-stage disease, since "these individuals are theoretically more likely to express high levels and greater variety of antibodies."

According to the researchers, the diagnostic accuracy of their assay exceeds that of other clinically available markers. Tissue polypeptide antigen has a diagnostic accuracy of 80%; CA19-9, 62%; carcinoembryonic antigen, 73%; squamous cell carcinoma antigen, 62%; and neuron-specific enolase, 63%.

LIMITATIONS

The researchers said one limitation of their study was that they did not exhaustively screen libraries for all possible markers. "Although we have not generated a comprehensive panel of antibodies and associated proteins we have obtained an inventory of markers that can distinguish NSCLC patient samples from control subject samples."

Future studies should focus on testing with early stage cancer and even with pre-cancer patient samples. "It would be extremely helpful if this antibody profiling technique can distinguish immune changes in precancer patients, since cancer can take many years to develop and the immune system may not recognize the changes long before current technology can," said Dr. Zhong.

—Karen L. Spittler

Reference
1. Zhong L, Hidalgo GE, Stromberg AJ, et al. Using protein microarray as a diagnostic assay for non–small cell lung cancer. Am J Respir Crit Care Med. 2005;172:1308-1314.

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