title: Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib.
abstract: OBJECTIVE
  The factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases; however, it was first discovered as a lung cancer-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status.
  
  
  METHODS
  Between September 2002 and September 2005, 41 patients with NSCLC were treated with gefitinib after having their serum KL-6 levels measured at Okayama University Hospital. EGFR mutations were analyzed by direct sequence methods.
  
  
  RESULTS
  The serum KL-6 levels ranged from 199 to 9080U/ml (median, 550U/ml), and 54% of 41 patients showed a level higher than the cut-off level of 500U/ml. The median progression-free survival (PFS) time and the median overall survival (OS) time were 4.7 months and 13.9 months, respectively. Multivariate analyses revealed that the elevated KL-6 level was an independent adverse prognostic factor for PFS (hazard ratio: 2.278, p=0.040) as well as OS (hazard ratio: 4.858, p=0.002) in NSCLC patients treated with gefitinib. The EGFR mutation status was analyzed in 22 patients (54%). Among those with wild-type EGFR, the patients with high serum KL-6 levels also had a worse survival than those within normal serum KL-6 levels (6.5 months versus 13.3 months, p=0.0194).
  
  
  CONCLUSIONS
  Our data suggest that NSCLC patients with high serum KL-6 levels tended to have a poor clinical outcome when treated with gefitinib.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanimoto
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; C060192:MUC1 protein, human; D018396:Mucin-1; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib