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R. Guijarro



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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): R. Guijarro

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.02-013 - The importance of immunoregulatory genes in non small cell lung cancer (ID 2461)

      12:54 - 13:11  |  Author(s): R. Guijarro

      • Abstract

      Background
      In non small cell lung cancer (NSCLC) it is of vital importance to develop biomarkers that allow us to assign a more accurate prognosis for patients in early stages, so we can apply the right treatment at the right time, preventing that the cancer reaches advanced stages when the cure rate is close to zero.

      Methods
      In this study we have selected a set of 9 genes related to immunoregulation and inflammation processes to analyze their relative expression on mRNA by qPCR in lung tissue samples from patients with NSCLC and resectable stage. CCL2 and CD1c genes showed a significantly lower expression in tumor tissue versus healthy tissue. After that, we analyzed the correlation between expression levels of these genes and relevant clinicopathological variables in the patients. Poorly differentiated tumors showed higher expression levels of CD209, CCL2, LGALS1 and LGALS2, whereas in smokers an increased expression of galectin LGALS1 was documented. Finally, survival analysis was performed using the Kaplan-Meier method to assess the utility of genes as prognostic biomarkers in this disease.

      Results
      In the subgroup of patients with squamous cell histology, those with lower levels of expression of CCL22 showed a significant increase in overall survival (OS) and progression-free survival (PFS). In our cohort of patients with resectable NSCLC, survival analyses showed that elevated levels of galectin LGALS2 and CCL2 chemokine are associated with a better prognosis in overall survival (OS) and progression-free survival (PFS).

      Conclusion
      The data obtained in our study provide further evidence about the necessity of tumors to manipulate the microenvironment around them as a prelude to progress and invade tissues.