Author of

• 11481

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  P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11495

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    P2.02-014 - Discovery of circulating protein biomarkers of lung dysplasia (ID 2481)

    13:11 - 13:28  |  Author(s): R. Keith
    • Abstract

    Background
    Endobronchial dysplasia is a premalignant lesion commonly found in current and former smokers. Identifying and treating these lesions before they progress to lung cancer may improve survival. The iloprost chemoprevention trial demonstrated that supplementation with the prostacyclin analog, iloprost, reduced histologic dysplasia in former smokers (Keith et al. Cancer Prev Res. 2011). However, accurate detection of dysplasia requires invasive bronchoscopy to collect multiple endobronchial biopsy samples. This study is the first step in generating blood-based markers of dysplasia to identify individuals at high risk for developing lung cancer and who could benefit from chemoprevention treatment.

    Methods
    Baseline serum samples (n=70) collected from current and former smokers enrolled in the iloprost chemoprevention trial were analyzed with the SOMAscan proteomic platform, which measures 1129 proteins with a median limit of detection of 40 fM and 5% CV. To characterize dysplasia, 6 standardized endobronchial sites, as well as any others that appeared suspicious by either white light or autofluorescence visualization, were biopsied from each study participant and scored by expert pathologists. Samples were stratified by worst biopsy score (Max) for proteomic analysis. Biomarkers correlating with Max pathology score were identified using principal component analysis (PCA), a multivariate technique to identify correlated variables, and the univariate, non-parametric Kolmogorov-Smirnov test (KS test). Serum proteins correlating with pulmonary function were also analyzed.

    Results
    Six proteins correlated with the progression of Max pathology. The change in serum level of these proteins ranged from 14-50% when comparing the lowest (n=16) and highest (n=39) Max pathology score groups. The proteins function in neoplastic progression, cell adhesion, inflammation and metabolic regulation. The protein with the most significant change (FDR correct p value = 0.05) regulates plasma clearance of steroid hormones. The serum protein most strongly correlated with lung function in our study was VEGFR2, which mediates VEGF induced endothelial proliferation and is known to be reduced in the lungs of smokers and patients with COPD and emphysema.

    Conclusion
    Our preliminary results of serum biomarkers associated with preneoplastic dysplasia warrant further study. If validated, this serum-based test to identify individuals who may benefit from chemopreventive intervention could impact lung cancer survival. This work was supported by NCI grants CA 58187 and CA165780.