Whole Genome Expression Profiling of Advance Stage Papillary Serous Ovarian Cancer Reveals Activated Pathways

Oncogene. 2004 Oct 21;23(49):8065-77. doi: 10.1038/sj.onc.1207959.

Abstract

Ovarian cancer is the most lethal type of gynecologic cancer in the Western world. The high case fatality rate is due in part because most ovarian cancer patients present with advanced stage disease which is essentially incurable. In order to obtain a whole genome assessment of aberrant gene expression in advanced ovarian cancer, we used oligonucleotide microarrays comprising over 40,000 features to profile 37 advanced stage papillary serous primary carcinomas. We identified 1191 genes that were significantly (P < 0.001) differentially regulated between the ovarian cancer specimens and normal ovarian surface epithelium. The microarray data were validated using real time RT-PCR on 14 randomly selected differentially regulated genes. The list of differentially expressed genes includes ones that are involved in cell growth, differentiation, adhesion, apoptosis and migration. In addition, numerous genes whose function remains to be elucidated were also identified. The microarray data were imported into PathwayAssist software to identify signaling pathways involved in ovarian cancer tumorigenesis. Based on our expression results, a signaling pathway associated with tumor cell migration, spread and invasion was identified as being activated in advanced ovarian cancer. The data generated in this study represent a comprehensive list of genes aberrantly expressed in serous papillary ovarian adenocarcinoma and may be useful for the identification of potentially new and novel markers and therapeutic targets for ovarian cancer.

MeSH terms

  • Carcinoma, Papillary / metabolism*
  • Carcinoma, Papillary / pathology
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • Gene Expression Profiling*
  • Genome
  • Humans
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / physiology
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Polymerase Chain Reaction
  • Signal Transduction

Substances

  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases