HGFK1 is associated with a better prognosis and reverses inhibition by gefitinib in NSCLC cases.
OBJECTIVE
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.


METHODS
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 resistant 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.
Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, China.
Xiao-Hui
XH
Zhou
Li-Na
LN
Tang
Lu
L
Yue
Da-Liu
DL
Min
Yi
Y
Yang
Jian-An
JA
Huang
Zan
Z
Shen
D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D018082:Kringles; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D047368:Tumor Burden
D000970:Antineoplastic Agents; D011799:Quinazolines; D050799:STAT5 Transcription Factor; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D000077156:Gefitinib