Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans
Annual rept. 15 Sep 2010-14 Sep 2011
CALIFORNIA UNIV LOS ANGELES
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During our first year of research, we demonstrated a localized field cancerization phenomenon on gene expression in the airway of patients with lung cancer, and we identified several pathways preferentially activated in the airway adjacent to tumors. In addition, we have identified markers of stem cells in the airway that may represent tumor-initiating cells of the airway and are evaluating profiles of these cells. We have identified Snail as a novel marker of stem cells in the airway that promote epithelial-mesenchymal transition. We have made a major technical advance in developing the methods required to use low quality and quantity laser capture microdissected material to sequence the transcriptome. This allows us to examine the gene expression profiles in premalignant lesions and compare it to the histologically normal airway epithelium and tumor. We have validated this approach and the data will allow us to identify novel pathways for lung carcinogenesis. All of these studies are identifying biomarkers that could be used for early lung cancer detection and pathways that are involved in field cancerization. Understanding this field cancerization and development of premalignant lesions is likely to shed light on novel pathways in lung carcinogenesis that could lead to diagnostic tests, therapies and cancer chemoprevention strategies for lung cancer.
- Anatomy and Physiology
- Medicine and Medical Research