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S. Gallach



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-030 - KRAS mutations in resectable NSCLC patients. Prognostic implications. (ID 2273)

      09:30 - 09:30  |  Author(s): S. Gallach

      • Abstract

      Background
      Development of Non-Small Cell Lung Cancer (NSCLC) requires multiple genetic and epigenetic alterations, with some differences according to etiology and histology. The most frequently mutated genes in these tumors are EGFR and KRAS (present mostly in adenocarcinomas), however, the prognostic value of KRAS mutations in NSCLC is still controversial.

      Methods
      Fresh tumor tissue samples (n=150) were obtained from resectable NSCLC patients. DNA was extracted by standard methods based in TriZol® and analyzed for KRAS mutational status by RTqPCR with ARMS technology and Scorpions probes. Non-parametric methods were used fos statistical analysis. Progression free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method (log-rank test). A p value ≤ 0.05 was considered statistically significant.

      Results
      Baseline characteristics of the patients were: median age, 64 years [26-82]; 86.0% male; 71.3% ECOG-PS 0; 40% adenocarcinomas (ADC). KRAS mutations were detected in 10.7% of the tumors (n= 150). Table 1 summarizes the mutations found in our cohort. In the subgroup of ADC + ADC-SCC samples, mutant KRAS represents 20% of the tumors. Considering only the never-smoker group of patients, 31.6% of the samples were mutated for KRAS. Our results showed that patients with KRAS mutated tumors had significantly shorter PFS than patients with wild type KRAS (11.633 vs 45.833 months, respectively, p= 0.043) and a trend to a shorter OS (23.067 vs 66.967 months, respectively, p= 0.074). Table 1: Distribution of KRAS mutations in our cohort

      n %
      Wild Type 134 89.3
      12SER 1 0.7
      12CYS 5 3.3
      12ASP 7 4.7
      12VAL 3 2.0
      TOTAL 150 100.0

      Conclusion
      KRAS gene mutation is a poor prognostic factor for PFS in our cohort of resectable NSCLC; therefore, the determination of the mutational status of KRAS gene might be implemented routinely in clinical practice. This work was supported in part, by a grant [RD06/0020/1024 and RD12/0036/0025] from Red Temática de Investigación Cooperativa en Cáncer, RTICC, and Instituto de Salud Carlos III (ISCIII).

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-037 - Expression of stemness factors OCT4 and NANOG in resectable non-small cell lung cancer. (ID 2695)

      09:30 - 09:30  |  Author(s): S. Gallach

      • Abstract

      Background
      Epithelial–mesenchymal transition (EMT) and expression of stemness features are key issues for tissue invasion and metastasis during cancer development. OCT4 and NANOG are homebox transcription factors essential to the self-renewal of stem cells and are expressed in several cancers. The role of OCT4/NANOG signaling in tumorigenesis and as biomarkers in non-small cell lung cancer (NSCLC) is still elusive.

      Methods
      mRNA was isolated from 177 frozen samples, corresponding to tumoral and normal parenchyma of NSCLC patients in resectable-stage. OCT4 and NANOG relative expression was determined by RTqPCR using hydrolysis probes. Expression levels were normalized using GUSB as endogenous housekeeping gene. Statistical significance was considered for p<0.05.

      Results
      Patient’s median age was 64 years [26-87], 87.6 % were males, 75.2 % presented performance status (PS=0) and 47.3% had squamous histology. We found a significant positive correlation between OCT4 and NANOG expression (r[2 ]=0.61 p<0.0001, Pearson test). Higher levels of expression of NANOG were related to poor differentiation grade (p= 0.04). Survival analysis revealed that there is a trend to a poorer progression free survival in the subgroup of patients with higher levels (> median) of expression of OCT4 levels

      Conclusion
      The transcription factor OCT4 may have a role as prognostic biomarker in resectable NSCLC. (Supported in part by ISCIII (PI12/02838), RTICC (RD12/0036/0025), Ministry of Economy and Competitiveness and SEOM Grants 2012)