New antibody profiling technique to test for lung cancer

American Thoracic Society journal news tips for November 2005 (second issue)

Biomedical scientists have revealed a new and promising antibody profiling technique that provides a high degree of early diagnostic accuracy for non-small cell lung cancer cases.

Their research was reported in the second issue of November 2005 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Li Zong, Ph.D. of the Division of Pulmonary and Critical Care Medicine, Chandler Medical Center, University of Kentucky, Lexington, along with five associates, has identified five non-small cell lung cancer-associated antibody proteins that achieved 90 percent sensitivity and 95 percent specificity in identifying cancerous versus non-cancerous patient samples.

(Sensitivity indicates the probability that results will be positive when disease is present. Specificity identifies the probability that results will be negative when disease is absent.)

According to the U.S. National Cancer Institute, 160,000 people die each year from lung cancer, making it the number one cause of cancer death in America. Smoking is the primary cause of the disease.

The authors state that presently only 25 percent of new cases of lung cancer are diagnosed at an early stage, when curative surgery is possible.

“Serum tumor markers have the potential of being incorporated into diagnostic and therapeutic practice to improve historically dismal outcomes in non-small cell lung cancer,” said Dr. Zong. “Potential uses include early detection or screening, differentiation of benign from malignant disease, differentiating histologies, defining stages and responses to therapy, and defining prognosis.

“These goals have generated considerable interest in identifying predictive tumor markers,” Dr. Zong continues. “Although a number of non-small cell lung cancer tumor markers are measurable and a combination of markers can enhance diagnostic value, limited sensitivity and specificity of these markers preclude their wide-spread clinical use. In context, tumor-associated antigens may expand the range of non-small cell lung cancer markers. Consistent with the knowledge that an antibody response to a single protein is unlikely to be a universal marker, we have been exploring methodology for efficiently identifying and measuring multiple tumor-associated antibodies.”

From a universe of 212 candidate markers, the researchers reduced the group to the five most predictive cancer-associated antibody proteins.

“Results show that five phage markers had significant ability to distinguish patient samples from normal control subjects in the training set, said Dr. Li.

Based on their results, they hope to develop a diagnostic assay to assist in early diagnosis of lung cancer.

During development, the researchers tested the proteins associated with predominately advanced-stage lung cancer since those cells were theoretically more likely to express both high levels of and a greater variety of antibodies.

In subsequent studies, they plan to test persons who have early-stage lung cancer against matched control subjects. They hope this will help them determine the ability of antibody profiling to distinguish benign from malignant disease in a group whose potentially cancerous nodules cannot clearly be determined radiographically.