Author of

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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
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12474

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    P3.06-034 - Dual-function protein APE1 is a novel biomarker to predict tumor response in Chinese patients with stages IIIB to IV non-small-cell lung cancer. (ID 2569)

    09:30 - 09:30  |  Author(s): Y. Xiong
    • Abstract

    Background
    More than 70% of patients with lung cancer are diagnosed with advanced-stage, with short survival times. The discovery of epidermal growth factor receptor (EGFR) mutations is a major scientific breakthrough; tyrosine kinase inhibitor (TKI) treatment for patients with EGFR mutations reported a median overall survival of more than 2 years. Nevertheless, chemotherapy has steadfastly remained the most validated therapies in non-small-cell lung cancer (NSCLC) not only for vast majority of patients without EGFR mutations, but for those with EGFR-TKI resistance. There are many influence factors in platinum resistance, among them DNA repair genes have been extensively explored. Excision repair cross complementing 1 (ERCC1) and/or breast cancer susceptibility gene 1 (BRCA1) is generally associated with sensitivity to platinum, but the results were inconclusive and controversial. Apurinic/apyrimidinic endonuclease 1 (APE1), a bifunctional AP endonuclease/redox factor, is important in DNA repair and redox signaling, may be associated with chemoresistance.

    Methods
    In total, 172 patients with advanced NSCLC who received platinum-based doublet chemotherapy, ages 34 to 84 years at diagnosis from 2007 to 2012 were enrolled into this study. We evaluated the impact of APE1, BRCA1, ERCC1 expression levels on response to platinum-based chemotherapy and median progression-free survival (mPFS) and/or median overall survival (mOS) outcomes, and protein expression levels were determined by immunohistochemistry (IHC).

    Results
    The mPFS was 8.8 months, mOS 12.8 months. A partial treatment response was found in 55 patients (31.98%). No significant association was found between BRCA1 protein expression and response rate, mPFS or mOS. Interestingly, patients whose tumors did not express APE1 had 50.00% response rate compared to 25.00% whose tumors expressed the protein (OR 0.34; 95% CI 0.17-0.69; P=0.002). Patients negative for APE1 had a significantly longer mPFS (10.3 vs. 8.0 months, P=0.016), but not mOS (17.1 vs. 10.9 months, P=0.263), than those positive for APE1. Patients negative for ERCC1 expression experienced better response to chemotherapy (OR 0.36; 95% CI 0.18-0.72; P=0.003), longer mPFS (9.8 vs. 6.8 months, P=0.001), and longer mOS (14.4 vs. 10.3 months, P=0.011). In particular, the expression of ERCC1 had a positive trend of correlation with APE1 expression (r[2]=0.23, P<0.01), and patients negative for both APE1 and ERCC1 had significantly higher response rate (OR 0.18; 95% CI 0.07-0.45; P<0.001), longer mPFS (12.0 vs. 6.8 months, P<0.001) and mOS (18.8 vs. 10.1 months, P=0.010), than those positive for both APE1 and ERCC1. Multivariate analysis adjusting for possible confounding factors showed that negative APE1 and/or ERCC1 expression was a significantly favorable factors for mPFS (HR 1.86, P=0.002 and HR 1.83, P=0.001; respectively) and mOS (HR 2.02, P=0.002 and HR 1.78, P=0.007; respectively).

    Conclusion
    The results suggest that dual-function protein APE1 may be a novel prognostic and predictive factor, and the combined detection of APE1 and ERCC1 expression might better individualize the efficacy of chemotherapy and improve survival in advanced NSCLC.