Sol and Judith Professor of Medicine, Director of Pulmonary and Critical Care Medicine, New York University School of MedicineView Slides
Lung cancer is the leading cause of cancer deaths in the U.S. at 160,000/year because most cases are diagnosed in later stages and the disease is histologically heterogeneous. New clinically effective diagnostic methods are urgently needed to identify lung cancer in earlier stages when surgical resection has the potential for curative therapy. Of concern is that the U.S. cigarette smoking rate increased from 19.8% in 2007 to 20.6% in 2008. Environmental carcinogens also cause DNA-adducts at “hot spots” in TP53 and KRAS that correlate with mutations. Furthermore, mutated receptors lead to up regulation of signaling pathways P13K and p38 kinases. CT-scan screening can identify non-calcified nodules in over half of high-risk smokers. A panel of blood biomarkers may distinguish malignant from benign nodules including auto-antibodies, anti-glycan antibodies, serum proteins, PBMC multiple gene expression or methylation of promoters. Using a new proteomics technology based on SOMAmers, modified DNA aptamers with very long dissociation rates, we conducted a multi-center study on 281 NSCLC and 1035 controls matched for age, gender, and smoking. After evaluating 813 proteins/subjects, a 12-protein signature achieved 91% sensitivity and 84% specificity with an AUC of 0.91 in the training set, and 89% sensitivity and 83% specificity in the testing set. A blood protein biomarker panel has potential for identifying individuals with a history of cigarette smoking who are at increased risk for early stage lung cancer.