title: Association between plasma hepatocyte growth factor and gefitinib resistance in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  It has been suggested that hepatocyte growth factor (HGF) and insulin-like growth factor binding protein (IGFBP)-3 are associated with gefitinib resistance in non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic roles of these proteins in NSCLC patients treated with gefitinib.
  
  
  METHODS
  Of 106 patients enrolled in a randomized phase II study of gefitinib, 97 had plasma samples available for ELISA testing. Of these samples, seven and eight, respectively, had HGF and IGFBP-3 values that could not be measured. Therefore, the correlations between clinical outcomes and plasma levels of HGF and IGFBP-3 were evaluated in 90 and 89 patients, respectively.
  
  
  RESULTS
  Plasma HGF levels were significantly higher in older patients, male patients, patients with squamous cell carcinoma, current smokers, and patients with epidermal growth factor receptor (EGFR) wild-type tumors. Low HGF levels were significantly associated with higher response rate, and longer progression-free survival (PFS) and overall survival (OS) irrespective of EGFR mutation status. In a multivariate analysis, the presence of EGFR mutations (P=0.002) and low HGF levels (P=0.031) were independently predictive of longer PFS, and an ECOG PS of 0 (P=0.001) and low HGF levels (P=0.002) were independently predictive of longer OS. No statistically significant differences were found for IGFBP-3.
  
  
  CONCLUSIONS
  High HGF levels are significantly associated with resistance to gefitinib and can be used as a predictive marker for the differential outcome of gefitinib treatment in NSCLC irrespective of EGFR mutation status.
authors: Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea. jymama@ncc.re.kr
authors: Ji-Youn
authors: JY
authors: Han
authors: Jin Young
authors: JY
authors: Kim
authors: Suk Hyung
authors: SH
authors: Lee
authors: Nam Jin
authors: NJ
authors: Yoo
authors: Byung Gil
authors: BG
authors: Choi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004351:Drug Resistance; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D054316:Biomarkers, Pharmacological; D018972:Insulin-Like Growth Factor Binding Protein 3; D011799:Quinazolines; D017228:Hepatocyte Growth Factor; D000077156:Gefitinib