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Y.S. Chang



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-024 - Prognostic value of RALA and RALB overexpression in KRAS mutant lung cancer (ID 2050)

      09:30 - 09:30  |  Author(s): Y.S. Chang

      • Abstract

      Background
      Oncogenic mutations of KRAS play important roles in cancer progression and resistance to chemotherapy in non-small cell lung cancer (NSCLC). Ras-related proteins, RALA and RALB, are members of the RAS superfamily of small GTPases and act as downstream effectors of KRAS. Therefore RAL proteins may be involved in cancer cell survival, invasion and metastasis. In this study, authors investigated the prognostic role of RALA and RALB overexpression in non-small cell lung cancer (NSCLC) patients with KRAS mutations.

      Methods
      Expression status of RALA and RALB in the tumor tissue of NSCLC patients whose tumor harbors KRAS mutations were evaluated by immunohistochemistry(n=12). In addition, we investigated 11 metastatic lung tumor tissue samples from KRAS mutant colorectal cancer patients. Predictive factors for survival were calculated using Kaplan-Meier estimator and Cox proportional hazards model.

      Results
      There was no statistically significant relation between RALA/RALB overexpression and KRAS mutation subtypes. However, RALB was frequently overexpressed in the tumor of advanced stageof NSCLC with KRAS mutation(p=0.015, χ[2]-test). Furthermore, the overall survival of the patients with RALB overexpression was significantly shorter than that of the patients without RALB overexpression (2.7 vs. 7.3 months, P<0.001; Mann-Whitney U test). In metastatic lung tumor tissues from KRAS mutant colorectal cancer patients, RALB protein overexpression showed only a trend toward shortened disease free survival.

      Conclusion
      RALB overexpression might be related to rapid disease progression and poor prognosis in NSCLC patients with KRAS mutations.

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    P2.22 - Poster Session 2 - Epidemiology, Etiology (ID 167)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.22-003 - BIM (BCL2L11) deletion polymorphism is one of major risk factors of Lung cancer in Korean population. (ID 847)

      09:30 - 09:30  |  Author(s): Y.S. Chang

      • Abstract

      Background
      BIM (BCL2L11), which encodes a BH3-only protein, is one of major pro-apoptotic factors that facilitate cell death. A 2,903-bp genomic deletion polymorphism in intron 2 of BIM showed 12.3% carrier frequency in East Asian population. This polymorphism results in expression of BIM isoforms lacking the pro-apoptotic BH3. We evaluated whether the presence of the BIM deletion polymorphism is a major risk factors of lung cancer in Korean population.

      Methods
      We designed 1:1 matched case-control study between lung cancer and control subjects. Lung cancer patients and age, gender and smoking status matched control subjects without other types of malignancies were prospectively enrolled from Feb. 2013 to now. Subjects under 18 years old and who denied to present informed consent were excluded. The presence of 2,903-bp genomic DNA deletion polymorphism in intron 2 of BIM were analyzed by PCR and validated by sequencing. BIM deletion polymorphism status and relationship with clinical and pathological parameters were analyzed using chi-square test, t-test, Kaplan-Meyer estimator, and Log-Rank test.

      Results
      There were no statistically significant differences in age, gender and smoking status between lung cancer and control subjects. Twenty-three out of 102 (22.5%) lung cancer patients revealed a BIM deletion polymorphism whereas 9 out of 75 (12%) control subjects showed polymorphism. The odd ratio for the association of BIM deletion polymorphism and lung cancer was 2.139 (p=0.076). Sixty-nine out of 102 (67.6%) lung cancer patients were male and 52 (51%) were smoker. Among them 97 (95%) were non-small cell lung cancer (NSCLC) and 5 (5%) were small cell lung cancer. Adenocarcinoma was the most common histological subtype accounting for 69 out of 97 (71%) in NSCLC. When lung cancer patients were categorized according to the presence of polymorphism status, there was no difference in the age between subjects with and without polymorphism (mean age; 63.3 vs. 63.4 year). Among the lung cancer patients harboring BIM deletion polymorphism, there were more female (9 out of 23, 39%) and non-smokers (15 out of 23, 65%) when compared to those without polymorphism showing 24 out of 79 (30%) female and 35 out of 79 (44%) non-smokers. The histological subtypes between the two groups were not significantly different. A total of 64 out of 102 lung cancer patients had been tested EGFR mutation status. The odd ratio for the association of BIM deletion polymorphism and EGFR activating mutation was 0.87. In lung cancer patients, the BIM deletion polymorphism did not have a statistically significant impact on the clinical outcome of the patients.

      Conclusion
      Our results indicate that BIM deletion polymorphism may be one of major lung cancer risk factors in Korean population. To strengthen our results, we are extending the sample size and are going to perform hierarchical analysis prospectively. To validate our results, we are performing a validation analysis with an external validation dataset from the national cohort.