Microarray-Based Oncogenic Pathway Profiling in Advanced Serous Papillary Ovarian Carcinoma

Introduction: 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. Methodology: A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, beta-Catenin, BRCA, E2F1, EGFR, ER, HER2, INF alpha, INF gamma, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNF alpha, and TGF beta 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 beta-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 beta-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