title: Individuality in FGF1 expression significantly influences platinum resistance and progression-free survival in ovarian cancer.
abstract: BACKGROUND
  Ovarian cancer is frequently advanced at presentation when treatment is rarely curative. Response to first-line platinum-based chemotherapy significantly influences survival, but clinical response is unpredictable and is frequently limited by the development of drug-resistant disease.
  
  
  METHODS
  We used qRT-PCR analysis to assess intertumour differences in the expression of fibroblast growth factor 1 (FGF1) and additional candidate genes in human ovarian tumours (n=187), and correlated individuality in gene expression with tumour histology, chemotherapy response and survival. We used MTT assays to assess platinum chemosensitivity in drug-sensitive and drug-resistant ovarian cell lines.
  
  
  RESULTS
  Marked intertumour differences in gene expression were observed, with each tumour having a unique gene expression profile. Nine genes, including FGF1 (P=1.7 × 10(-5)) and FGFR2 (P=0.003), were differentially expressed in serous and nonserous tumours. MDM2 (P=0.032) and ERBB2 (P=0.064) expression was increased in platinum-sensitive patients, and FGF1 (adjusted log-rank test P=0.006), FGFR2 (P=0.04) and PDRFRB expression (P=0.037) significantly inversely influenced progression-free survival. Stable FGF1 gene knockdown in platinum-resistant A2780DPP cells re-sensitised cells to both cisplatin and carboplatin.
  
  
  CONCLUSIONS
  We show for the first time that FGF1 is differentially expressed in high-grade serous ovarian tumours, and that individuality in FGF1 expression significantly influences progression-free survival and response to platinum-based chemotherapy.
authors.affiliation: Division of Cancer Research, Medical Research Institute, University of Dundee, UK. g.smith@dundee.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Smith
authors.forename: M T H
authors.initials: MT
authors.lastname: Ng
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
authors.forename: C S
authors.initials: CS
authors.lastname: Herrington
authors.forename: C
authors.initials: C
authors.lastname: Gourley
authors.forename: M J
authors.initials: MJ
authors.lastname: Ferguson
authors.forename: C R
authors.initials: CR
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D016220:Fibroblast Growth Factor 1; D016190:Carboplatin; D002945:Cisplatin