Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans
Abstract
During our third year, we found that the transcriptomic architecture of the adjacent airway field cancerization in NSCLC is comprised of markers that identify lung cancer among smokers as well as gradient expression patterns that recapitulate tumor profiles, and thus, provides additional insights into NSCLC biology and the development of molecular tools for the detection of the malignancy. Furthermore, we studied in detail the functional roles of LAPTM4B, a putative oncogene that we identified as a field cancerization marker, in lung cancer pathogenesis. We found that LAPTM4B promotes growth of lung cancer cells in soft agar, is associated with smoking and worse overall survival, protects cells from serum deprivation-induced growth inhibition and positively controls the autophagic response and the NRF2 transcription factor during cellular stress. Furthermore, using a novel molecular spatial mapping approach, we identified gene sets, in patients with lung cancer, which decrease in enrichment with larger distance from the tumor as well as those that persist up to the nasal epithelium. These data point to specific tumor associated profiles that are enriched in the nasal epithelium and, thus, comprise readily accessible markers for lung cancer detection that will be further refined and validated in aim 3 of the study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA598411
Entities
People
- Humam Kadara
- Ignacio I. Wistuba
Organizations
- The University of Texas MD Anderson Cancer Center