079 Identification of Genes Associated With Ovarian Cancer Metastasis Using Microarray Expression Analysis

The transition from early to advanced stage ovarian cancer is a critical determinant of survival, though little is known about the molecular underpinnings of ovarian metastasis. We applied Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie the development of omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (p < 0.01), and 20/56 (36%) differentially expressed genes have previously been implicated in metastasis, cell motility or cytoskeletal function. Ten of 56 genes (18%) are involved in p53 gene pathways. Bayesian statistical tree analysis was applied to validate the significance of the gene expression patterns, and identified 27 genes that could accurately predict tumor site (ovary vs. omentum) in 87% of cases in cross-validation studies. Nine of these 27 (33%) genes (GRP135, FHL-2, GA, LAMC2, MAGE-A10, CDK5, RPS6KB1, AIM2, and SLIT3) have previously been shown to be involved in oncogenesis, and 10/27 (37%) genes (LAMC2, APOBEC2, FHL, STAR, PARD6B, ELAVL1, ANGPT1, CDK5, RPS6KB1, and RFXAP) have been implicated in p53 pathways. Using genome-wide expression technology and novel statistical and gene pathway analyses we have identified a distinct genetic profile that underlies omental metastasis from epithelial ovarian cancer. Many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis and p53 gene networks.