Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays.
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. We performed global gene expression analysis in 13 primary epithelial ovarian cancer tissues including 5 primary chemosensitive tumors and 8 primary chemoresistant tumors using Affymetrix HGU133A microarray. The gene expression patterns of chemosensitive tumors were compared with those of chemoresistant tumors using fold change. Validity of microarray results was examined by semiquantitative RT-PCR. We identified over 320 genes differentially expressed in chemoresistant epithelial ovarian cancer (> or = twofold). Upregulated genes in chemoresistant tumors included cell cycle regulating genes (TOP2A, BCAT1, CDCA8, CCNA2, CENPE), and genes with previously known mechanisms in tumorigenesis (S100A9, APOA1, RNF125, IFI16). Downregulated genes in chemoresistant tumors included genes related to cell adhesion (MUC5B, CITED2), transcription regulating genes (FOXD1, MAD1L1, PAX2), genes involving signal transduction (SOSTDC1, SNX1, SFRP1, FOXA2, PLK2), and stress protein gene (TP53AP1). These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. This type of molecular profiling could provide a basis for additional functional studies.
Ju
Woong
W
Department of Obstetrics and Gynecology and Medical Research Institute, College of Medicine, Ewha Womans University, Seoul, South Korea. goodmorning@ewha.ac.kr
Yoo
Byong Chul
BC
Kim
Il-Jin
IJ
Kim
Jae Weon
JW
Kim
Seung Cheol
SC
Lee
Hyo Pyo
HP
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins
D000951:Antigens, Neoplasm; D040502:Calgranulin B; D004268:DNA-Binding Proteins; C524578:MUC5B protein, human; D055257:Mucin-5B; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human