title: Predictive and prognostic value of human copper transporter 1 (hCtr1) in patients with stage III non-small-cell lung cancer receiving first-line platinum-based doublet chemotherapy.
abstract: BACKGROUND
  Recent studies have shown that human copper transporter 1 (hCtr1), the major copper influx transporter, is involved in the transport of platinum-based antitumor agents. We investigated the predictive and prognostic values of hCtr1, and copper efflux transporters ATP7A and ATP7B, in patients with locally advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy.
  
  
  METHODS
  From 2004 to 2009, we identified 54 consecutive stage III NSCLC patients who underwent first-line platinum-based doublet chemotherapy. Immunohistochemical studies of hCtr1, ATP7A and ATP7B on the paraffin-embedded pre-treatment tumor samples were performed and correlated with chemotherapy response and survival.
  
  
  RESULTS
  Overexpression of hCtr1, ATP7A and ATP7B were observed in 68%, 48% and 74% of the participants, respectively. hCtr1 overexpression was associated with better chemotherapy responses (P<0.01); whereas ATP7A and ATP7B were not. Patients with hCtr1 overexpressing tumors had better progression-free survival (PFS) and overall survival (OS) (P=0.01 and 0.047, respectively). In multivariate analyses for chemotherapy response and PFS, only hCtr1 overexpression emerged as a favorable independent predictive and prognostic factor (all P<0.01).
  
  
  CONCLUSIONS
  This is the first report to state that hCtr1 is not only an independent predictor of platinum-based chemotherapy response but also a prognostic factor in stage III NSCLC.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Helen H W
authors.initials: HH
authors.lastname: Chen
authors.forename: Jiang-Jou
authors.initials: JJ
authors.lastname: Yan
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Chen
authors.forename: Macus Tien
authors.initials: MT
authors.lastname: Kuo
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lai
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Lai
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D027682:Cation Transport Proteins / Q000032:analysis* / Q000502:physiology; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D055808:Drug Discovery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D009944:Organoplatinum Compounds; C490079:SLC31A1 protein, human; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases