HGFK1 is Associated with a Better Prognostis and Reverses Inhibition by Gefitinib in NSCLC Cases

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 alphachain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor inhepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not beenreported to date. <br/><b>Method</b>: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advancedNSCLC to investigate the impact of HGFK1 on survival. <br/><b>Results</b>: Results revealed 33 (30.1%) patients wereclassified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but notwith lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expressionand tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that bothoverall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer thanthose of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinibinhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreasedphosphorylation of ERK and STAT5. <br/><b>Conclusions</b>: HGFK1 may be a useful prognostic factor of advancedNSCLC patients and a potential drug for gefitinib resistant patients.