Author of

• 10525

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  P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10539

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    P1.02-014 - The Gene-Expression Profiles in advanced lung Adenocarcinoma associated with Wood Smoke or tobbacco exposure are different in brain metastasis (ID 1970)

    09:30 - 16:30  |  Author(s): G.M. Celis
    • Abstract

    Background
    Environmental factors contributed toward lung carcinogenesis. Tobacco-smoking is the major etiological factor related with lung cancer in 90% in the world compared with Mexico with 66% of cases. In previous works we have demonstrated that other factors such as chronic exposure to wood smoke (WSE) are related to non-small-cell lung cancer (NSCLC) and it´s clinically and pathologically different from lung cancer arisen from tobacco-exposure, regarding on tumor histology, mutation profiles, brain metastasis incidence, response rate and overall survival. This work is aimed to estimate expression profiles related WSE on adenocarcinoma histology associated to pathological mechanisms that differ from other carcinogenic factors, such as tobacco exposure.

    Methods
    This study used clinical, longitudinal, prospective and observational. From January 2008 to June 2011, patients were admitted in Cancerology Institute with lung adenocarcinoma in stage IV, eligible for the inclusion. Clinical variables, WSE, gender and age. WSE was defined to being exposed to fumes by burning wood in fireplaces and wood stoves for five years for at least 4 hours per day. The WSE index was calculated multiplying the number of daily hours exposed by years of exposure. Collaboration agreements with the Institute of Medical Genomics and approved within the Health Research Sectorial Fund, CONACyT-México (SALUD-2009-01-115552). Primary biopsies were taken by guided tru-cut needle by tomography. Samples were analyzed by the Pathology for histological/quantification of neoplasic celularity, and stored at -80°C. RNA was extracted from tumor biopsies. RNA integrity (RIN>6) was analyzed using the Agilent 6000. We used an Affymetrix Human GeneChip® 1.0 ST. Two-Cycle Target Labeling was followed for microarrays. Analysis was done by Affymetrix console and “R” software language. Matrices employ 29 microarrays with experimental contrasts. Differential expressed genes were analyzed by linear model that analyze contrasts between experimental contrasts. The Partek Genomic Software 4 and SAM (Significant Analysis) was used for microarray comparisons and integration of genomic data.

    Results
    Using computational genomics using fold changes and confiability data we found differences in genomic expression. In brain metastasis (BM) patients the Fold Change values >1 shows 6 upregulated and 11 downregulated genes compared with or without WSE. Patients without BM the Fold Change values >1 shows 90 downregulated and 7 upregulated genes with or without WSE. Prior both analysis were confirmed with B statistics data (significant value ≥0). No difference were found using computational Genomics SAMS (False discovery rate), neither PARTEK (p-value, fold change), on gene expression evaluation.

    Conclusion
    Our results demonstrate that gene expression profiles are different in advanced lung adenocarcinoma patients with brain metastasis with or without WSE. These results could be used for predictive models related with BM in advanced lung cancer. The best genomic statistical value was obtained with Affymetrix console and “R” software language in this work. These results must be confirmed by increasing the experimental samples and validating in an independent cohort by PCR.