Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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HGFK1 is Associated with a Better Prognostis and Reverses Inhibition by Gefitinib in NSCLC Cases

  • Zhou, Xiao-Hui (Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University) ;
  • Tang, Li-Na (Department of Oncology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University) ;
  • Yue, Lu (Cancer Center, the Medical School, Hospital of Qingdao University) ;
  • Min, Da-Liu (Department of Oncology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University) ;
  • Yang, Yi (Department of Thoracic Surgery, Shanghai 6th People's Hospital, Shanghai Jiao Tong University) ;
  • Huang, Jian-An (Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University) ;
  • Shen, Zan (Department of Oncology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University)
  • Published : 2012.04.30
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Abstract

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

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References

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