title: Microarray-based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma.
abstract: BACKGROUND
  The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome.
  
  
  METHODS
  A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, β-Catenin, BRCA, E2F1, EGFR, ER, HER2, INFα, INFγ, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNFα, and TGFβ and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464) to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS) were analysed.
  
  
  RESULTS
  The GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation score were associated with survival outcome (p = 0.002;p = 0.004). Increased activations of β-Catenin (p = 0.0009), E2F1 (p = 0.005), PI3K (p = 0.003) and p63 (p = 0.05) were associated with more favourable clinical outcome and were consistently correlated with three prognostic gene signatures.
  
  
  CONCLUSIONS
  Oncogenic pathway profiling of advanced serous ovarian tumours revealed that increased β-Catenin, E2F1, p63, PI3K, PR and RAS-pathway activation scores were significantly associated with favourable clinical outcome. WHR, GGI and IGS scores were unexpectedly increased in chemosensitive tumours. Earlier studies have shown that WHR, GGI and IGS are strongly associated with proliferation and that high-proliferative ovarian tumours are more chemosensitive. These findings may indicate opposite confounding of prognostic versus predictive factors when studying biomarkers in epithelial ovarian cancer.
authors.affiliation: Translational Cancer Research Unit, St Augustinus GZA Hospitals, Antwerp, Belgium.
authors.forename: Xuan Bich
authors.initials: XB
authors.lastname: Trinh
authors.forename: Wiebren A A
authors.initials: WA
authors.lastname: Tjalma
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Peter B
authors.initials: PB
authors.lastname: Vermeulen
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Peeters
authors.forename: Dimcho
authors.initials: D
authors.lastname: Bachvarov
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.forename: Els M
authors.initials: EM
authors.lastname: Berns
authors.forename: Jozien
authors.initials: J
authors.lastname: Helleman
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Laere
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Dam
mesh_terms: D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A