Researchers from Boston University School of Medicine (BUSM) have identified a gene expression marker that distinguishes smokers with lung cancer from smokers without the disease. The findings, reported in the March 1, 2007 advanced on-line edition of Nature Medicine, may have immediate clinical relevance and public health impact.
Lung cancer is the leading cause of death from cancer in the United States and the world. The high mortality rate (80-85 percent with five years) results in part from a lack of effective tools to diagnose the disease at an early stage. As a result, most patients require invasive diagnostic tests which delay treatment and generate additional costs and risk for complications.
Given that cigarette smoke creates injury throughout the airway, the researchers sought to determine if gene expression in normal large-airwave epithelial cells obtained during a bronchoscopy (a relatively non-invasive diagnostic test) from smokers with a suspicion of lung cancer could be used as a lung cancer biomarker. Using Affymetrix HG-U133A microarrays, the researchers performed gene-expression profiling of these airway cells and identified an 80-gene biomarker that distinguished smokers with and without lung cancer.
The researchers then went on to test the biomarker on an additional 52 patients with an accuracy of 83 percent. They also received similar results on a prospective series of subjects (35 patients) independently obtained from five medical centers. The researchers found the biomarker approximately 90 percent sensitive for identifying stage 1 lung cancer, a potentially curable stage of disease.
“Our study has identified an airway gene-expression biomarker that will impact the diagnostic evaluation of smokers with suspect lung cancer. Our data also suggests that combining cytopathology of lower airway cells with the gene expression biomarker improves the diagnostic sensitivity of the overall bronchoscopy procedure from 53 to 95 percent,” said lead author Avrum Spira, MD, MSc, an assistant professor of medicine and pathology at BUSM.
This study was supported by the Doris Duke Charitable Foundation, US National Institutes of Health/National Institute of Environmental Health Sciences and National Institutes of Heal/National Cancer Institute.