Du Fengkun, Li Yan, Zhang Wensheng, Kale Shubha P, McFerrin Harris, Davenport Ian, Wang Guangdi, Skripnikova Elena, Li Xiao-Lin, Bowen Nathan J, McDaniels Leticia B, Meng Yuan-Xiang, Polk Paula, Liu Yong-Yu, Zhang Qian-Jin
Department of Biology, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
College of Chemistry & Environmental Science, Hebei University, Baoding, Hebei Province 071002, China.
Tumour Biol. 2016 Aug;37(8):11147-11162. doi: 10.1007/s13277-015-4518-4. Epub 2016 Mar 2.
Patients with advanced epithelial ovarian cancer often experience disease recurrence after standard therapies, a critical factor in determining their five-year survival rate. Recent reports indicated that long-term or short-term survival is associated with varied gene expression of cancer cells. Thus, identification of novel prognostic biomarkers should be considered. Since the mouse genome is similar to the human genome, we explored potential prognostic biomarkers using two groups of mouse ovarian cancer cell lines (group 1: IG-10, IG-10pw, and IG-10pw/agar; group 2: IG-10 clones 2, 3, and 11) which display highly and moderately aggressive phenotypes in vivo. Mice injected with these cell lines have different survival time and rates, capacities of tumor, and ascites formations, reflecting different prognostic potentials. Using an Affymetrix Mouse Genome 430 2.0 Array, a total of 181 genes were differentially expressed (P < 0.01) by at least twofold between two groups of the cell lines. Of the 181 genes, 109 and 72 genes were overexpressed in highly and moderately aggressive cell lines, respectively. Analysis of the 109 and 72 genes using Ingenuity Pathway Analysis (IPA) tool revealed two cancer-related gene networks. One was associated with the highly aggressive cell lines and affiliated with MYC gene, and another was associated with the moderately aggressive cell lines and affiliated with the androgen receptor (AR). Finally, the gene enrichment analysis indicated that the overexpressed 89 genes (out of 109 genes) in highly aggressive cell lines had a function annotation in the David database. The cancer-relevant significant gene ontology (GO) terms included Cell cycle, DNA metabolic process, and Programmed cell death. None of the genes from a set of the 72 genes overexpressed in the moderately aggressive cell lines had a function annotation in the David database. Our results suggested that the overexpressed MYC and 109 gene set represented highly aggressive ovarian cancer potential biomarkers while overexpressed AR and 72 gene set represented moderately aggressive ovarian cancer potential biomarkers. Based on our knowledge, the current study is first time to report the potential biomarkers relevant to different aggressive ovarian cancer. These potential biomarkers provide important information for investigating human ovarian cancer prognosis.
晚期上皮性卵巢癌患者在接受标准治疗后常出现疾病复发,这是决定其五年生存率的关键因素。最近的报告表明,长期或短期生存与癌细胞的不同基因表达有关。因此,应考虑鉴定新的预后生物标志物。由于小鼠基因组与人类基因组相似,我们使用两组在体内表现出高度和中度侵袭性表型的小鼠卵巢癌细胞系(第1组:IG-10、IG-10pw和IG-10pw/琼脂;第2组:IG-10克隆2、3和11)探索潜在的预后生物标志物。注射这些细胞系的小鼠具有不同的生存时间和比率、肿瘤形成能力以及腹水形成能力,反映了不同的预后潜力。使用Affymetrix小鼠基因组430 2.0芯片,两组细胞系之间共有181个基因差异表达(P<0.01),差异倍数至少为两倍。在这181个基因中,分别有109个和72个基因在高度侵袭性和中度侵袭性细胞系中过表达。使用Ingenuity Pathway Analysis(IPA)工具对这109个和72个基因进行分析,发现了两个与癌症相关的基因网络。一个与高度侵袭性细胞系相关,与MYC基因有关,另一个与中度侵袭性细胞系相关,与雄激素受体(AR)有关。最后,基因富集分析表明,高度侵袭性细胞系中过表达的89个基因(共109个基因)在David数据库中有功能注释。与癌症相关的重要基因本体(GO)术语包括细胞周期、DNA代谢过程和程序性细胞死亡。在中度侵袭性细胞系中过表达的72个基因中,没有一个基因在David数据库中有功能注释。我们的结果表明,过表达的MYC和109个基因集代表高度侵袭性卵巢癌潜在生物标志物,而过表达的AR和72个基因集代表中度侵袭性卵巢癌潜在生物标志物。据我们所知,本研究首次报道了与不同侵袭性卵巢癌相关的潜在生物标志物。这些潜在生物标志物为研究人类卵巢癌预后提供了重要信息。