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S.K. Kim



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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): S.K. Kim

      • 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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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-001 - Transglutaminase 2 can be predictive of epidermal growth factor receptor tyrosine kinase inhibitor efficacy and cytotoxic chemotherapy success in non-small cell lung cancer (ID 96)

      09:30 - 09:30  |  Author(s): S.K. Kim

      • Abstract

      Background
      Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and the constitutive activation of NF-κB, a pro-inflammatory transcription factor. We investigated the association of the EGFR-TKI or cytotoxic chemotherapy clinical efficacy with transglutaminase 2 and NF-ĸB expression in non-small cell lung cancer (NSCLC).

      Methods
      TG2 and NF-ĸB expression was immunohistochemically studied in 120 patients with NSCLC who received an operation. Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the effect of TG2 and NF-ĸB expression on chemotherapy clinical efficacy.

      Results
      Median age of patients was 64 years (41–82). There were 102 (85%) cases of adenocarcinoma and 18 patients (15%) had other histologies. Eight patients received adjuvant chemotherapy, 29 received platinum-based doublet chemotherapy and another 29 patients received EGFR-TKI. Smoking status was as follows: 25 current, 16 former and 79 never. There were 55 patients with an EGFR mutation. TG2 median value was 50 (0 to 300) and NF-kB median value was 20 (0 to 240). Response to platinum-based doublet was as follows: Overall response rate (ORR) was 13.8% and disease control rate (DCR) was 69% (Complete response (CR) 0%, partial response (PR) 13.8%, stable disease (SD) 55.2% and progressive disease (PD) 24.1%). Responses to EGFR-TKI was as follows: ORR was 24.1% and DCR was 58.6% (CR 3.4%, PR 20.7%, SD 34.5% and PD 34.5%). Among the 88 patients who received adjuvant chemotherapy, disease-free survival (DFS) did not differ between the low and high TG2 groups. Among patients (n=29) who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was significantly longer in the low TG2 group when compared with the high TG2 group (34.0 versus 15.0 months, p = 0.003). Among those who received EGFR-TKI (n=29) (first line 7, second line 18, third line 3, fourth line 1), PFS was significantly longer in the low TG2 group when compared with high TG 2 group (11.0 versus 2.0 months, p = 0.013). In patients with EGFR wild-type mutations treated with EGFR-TKI, progression free survival was longer in patients with low TG2 expression (9.0 vs 2.0 months, p=0.013).

      Conclusion
      This study suggests that TG2 expression can be predictive of success of cytotoxic chemotherapy and EGFR-TKI for patients with non-small cell lung cancer, particularly in patients with EGFR wild-type mutations.