title: Upregulated FGFR1 expression is associated with the transition of hormone-naive to castrate-resistant prostate cancer.
abstract: BACKGROUND
  Prostate cancer (PC) represents a global health issue. Treatment for locally advanced and metastatic PC remains unsatisfactory. The androgen receptor (AR) has been validated in having a key role in both naïve and castrate-resistant PC (CRPC). However, the significance of other signalling pathways in CRPC is less well validated.
  
  
  METHODS
  To gain a better insight into the molecular signalling cascades involved in clinical CRPC, we performed gene expression profiling using the Illumina DASL assay and studied matched hormone-naive (HN) and CR prostate tumours (n=10 pairs). Ingenuity Pathways Analysis (IPA) was used to identify potential networks involved, and further validation was performed in in vitro cell models and clinical tumours.
  
  
  RESULTS
  Expression of 50 genes was significantly different between HN and CRPC. IPA revealed two networks of particular interest, including AR and FGFR1, respectively. FGFR1 expression was confirmed to be significantly upregulated in CRPC (P ≤ 0.005), and abnormal FGFR1 expression was associated with shorter time to biochemical relapse in HNPC (P=0.006) and less favourable disease-specific survival in CRPC (P=0.018).
  
  
  CONCLUSIONS
  For the first time, our gene expression profiling experiment on archival tumour materials has identified upregulated FGFR1 expression to be associated with PC progression to the CR state.
authors.affiliation: Solid Tumour Target Discovery Group, Northern Institute for Cancer Research, Newcastle University, Newcastle NE2 4HH, UK.
authors.forename: K
authors.initials: K
authors.lastname: Armstrong
authors.forename: I
authors.initials: I
authors.lastname: Ahmad
authors.forename: G
authors.initials: G
authors.lastname: Kalna
authors.forename: S S
authors.initials: SS
authors.lastname: Tan
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: C N
authors.initials: CN
authors.lastname: Robson
authors.forename: H Y
authors.initials: HY
authors.lastname: Leung
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000494:pharmacology*; D002369:Castration; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics; D012008:Recurrence; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000726:Androgen Antagonists; D011944:Receptors, Androgen; D007987:Gonadotropin-Releasing Hormone; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1