Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma.
Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma.
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DOI：
10.1186/1471-2407-10-576
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发表时间：
2010-10-22
期刊：
影响因子：
3.8
通讯作者：
Shick WA
中科院分区：
文献类型：
--
作者：
Kim YS;Hwan JD;Bae S;Bae DH;Shick WA
大多数卵巢癌患者被诊断为晚期(即III-IV期)，这与预后不良有关。采用一种新的差异显示方法--ACP系统筛选III期卵巢浆液性癌与正常组织的差异表达基因(DEG)。通过聚类分析和生存分析，找出了可用于Ⅲ期浆液性卵巢癌诊断和预后的标志物的潜在靶点。应用ACP逆转录聚合酶链式反应(RT-PCR)技术检测III期浆液性卵巢癌患者的DIGs。用实时定量聚合酶链式反应对ACP系统鉴定的DEG进行确认。根据实时定量聚合酶链式反应获得的基因表达谱进行聚类分析，采用Kaplan-Meier法和COX比例风险模型进行生存分析，比较耐药组和敏感组的基因表达结果。以ACP为基础的逆转录聚合酶链式反应技术在III期浆液性卵巢癌患者中共鉴定出114个DEG。与凋亡抑制过程相关的DEGS往往是上调的克隆，而与免疫反应相关的DEGS往往是下调的克隆。通过实时定量聚合酶链式反应获得的基因表达谱的聚类分析揭示了两组截然不同的DEG。也就是说，SSBP1、IFI6 DDT、IFI27、C11orf92、NFKBIA、TNXB、NEAT1和TFG等基因在大多数患者中上调，而LAMB2、XRCC6、MEF2C、RBM5、Foxp1、NUDCP2、LGALS3、TMEM185A和C1S基因在大多数患者中下调。生存分析显示，DDAH2、RNaseK、TCEAL2等基因表达上调可能与预后不良有关。此外，当RNaseK、Foxp1、LAMB2和MRVI1等基因上调时，化疗耐药患者的预后将非常差。以ACP为基础的逆转录聚合酶链式反应技术成功、可靠地鉴定了III期卵巢浆液性癌患者的DIGs。这项研究中确定的DEGS可能有助于预测III期浆液性卵巢癌患者的预后，并为开发新的治疗方案提供靶点。
Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such as RNase K, FOXP1, LAMB2 and MRVI1 were up-regulated. The DEGs in patients with stage III serous ovarian cancer were successfully and reliably identified by the ACP-based RT PCR technique. The DEGs identified in this study might help predict the prognosis of patients with stage III serous ovarian cancer as well as suggest targets for the development of new treatment regimens.
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