Donninger Howard, Bonome Tomas, Radonovich Mike, Pise-Masison Cynthia A, Brady John, Shih Joanna H, Barrett J Carl, Birrer Michael J
Department of Cell and Cancer Biology, National Cancer Institute, Rockville, MD 20850, USA.
Oncogene. 2004 Oct 21;23(49):8065-77. doi: 10.1038/sj.onc.1207959.
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.
在西方世界,卵巢癌是最致命的妇科癌症类型。其高病死率部分归因于大多数卵巢癌患者就诊时已处于晚期,而晚期疾病基本无法治愈。为了对晚期卵巢癌中异常基因表达进行全基因组评估,我们使用了包含4万多个特征的寡核苷酸微阵列,对37例晚期乳头状浆液性原发性癌进行分析。我们鉴定出1191个基因,这些基因在卵巢癌标本与正常卵巢表面上皮之间存在显著差异(P < 0.001)。通过对14个随机选择的差异调节基因进行实时逆转录聚合酶链反应(RT-PCR),验证了微阵列数据。差异表达基因列表包括参与细胞生长、分化、黏附、凋亡和迁移的基因。此外,还鉴定出许多功能尚待阐明的基因。将微阵列数据导入PathwayAssist软件,以识别参与卵巢癌肿瘤发生的信号通路。基于我们的表达结果,一条与肿瘤细胞迁移、扩散和侵袭相关的信号通路被确定在晚期卵巢癌中被激活。本研究产生的数据代表了浆液性乳头状卵巢腺癌中异常表达基因的综合列表,可能有助于识别卵巢癌潜在的新标记物和治疗靶点。