Identification of genes with differential expression in platinum-resistant epithelial ovarian cancer using high-density oligonucleotide microarrays.

B96

Objective : A major obstacle in treatment of epithelial ovarian cancer is chemoresistance. The aim of this study was to determine whether distinct gene expression profiles are associated with chemoresistance in epithelial ovarian carcinoma. Methods : We performed global gene expression analysis in 13 primary epithelial ovarian cancer tissues including 5 primary chemo-sensitive tumors and 8 primary chemo-resistant tumors using Affymetrix HG-U133A microarray. The gene expression patterns of chemo-sensitive tumors were compared with those of chemo-resistant tumors using fold-change. Validity of microarray results was examined by semiquantitative RT-PCR. Results : We identified over 320 genes differentially expressed in chemo-resistant epithelial ovarian cancer (≥ 2-fold). Up-regulated genes in chemo-resistant tumors included cell cycle regulating genes (TOP2A, BCAT1, CDCA8, CCNA2, CENPE), and genes with previously known mechanisms in tumorigenesis(S100A9, APOA1, RNF125, IFI16). Down-regulated genes in chemo-resistant tumors included genes related to cell adhesion(MUC5B, CITED2), transcription regulating genes(FOXD1, MAD1L1, PAX2), genes involving signal transduction(SOSTDC1, SNX1, SFRP1, FOXA2), and stress protein gene(TP52AP1). Conclusions : These data show that gene expression profiling can discriminate primary chemo-resistant from primary chemo-sensitive ovarian cancers. This type of molecular profiling could provide a basis for additional functional studies.