title: Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer.
abstract: BACKGROUND
  The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. Thus, c-Met status during EGFR-TKI therapy should receive much attention.
  
  
  RESULTS
  Forty-nine patients were selected as training cohort and 52 cases as validation cohort. With disease progression, IHC results showed that 37 (75.5%) of the patients were tissue c-Met-negative, and 12 (24.5%) were tissue c-Met-positive. There was a statistically significant difference in the dynamic change in soluble c-Met between the tissue c-Met-negative and c-Met-positive groups (P = 0.002). Patients with a baseline soluble c-Met level >766 ng/ml showed inferior median progression-free survival (PFS; 10.2 vs. 14.0 months; P = 0.003) after EGFR-TKI treatment. Multivariate Cox proportional hazards model analyses demonstrated that the soluble c-Met level was an independent prognostic factor for PFS after EGFR-TKI treatment (P = 0.009; hazard ratio: 3.583; 95% confidence interval: 1.379-9.312). In the validation cohort, patients with soluble c-Met levels >766 ng/ml were also determined to have significant short median PFS after EGFR-TKI treatment (6.8 vs. 14.5 months, P < 0.001).
  
  
  METHODS
  We retrospectively investigated the dynamic change in the soluble c-Met level in plasma and its relationship with clinical outcomes of EGFR-TKI therapy in advanced NSCLC. Immunohistochemistry (IHC) was used to assess the expression of c-Met in the resistant tissue. Plasma c-Met levels were assayed in duplicate using a human soluble c-Met quantitative enzyme-linked immunosorbent assay (ELISA) kit.
  
  
  CONCLUSIONS
  Quantitatively determining the soluble c-Met level in plasma by ELISA might provide a non-invasive and sensitive method to predict EGFR-TKI prognosis.
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.|Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Gao
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Wei-Bang
authors.initials: WB
authors.lastname: Guo
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Lou-Ying
authors.initials: LY
authors.lastname: Gou
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Dong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met
keywords: EGFR-TKI; NSCLC; soluble c-Met