• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >Prognostic Biomarker Identification Through Integrating the Gene Signatures of Hepatocellular Carcinoma Properties
【24h】

Prognostic Biomarker Identification Through Integrating the Gene Signatures of Hepatocellular Carcinoma Properties

机译：通过整合肝细胞癌基因特征的基因特征来鉴定生物标志物的预后。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Highlights ? Eleven gene signatures have promising values for the OS prediction of HCC patients who undergo the surgical treatments. ? Prediction results for the 11 gene signatures were in moderate concordance, and genes included were functionally linked. ? CDK1 is an independent prognostic biomarker and a potential therapeutic target for HCC patients. Various gene signatures for hepatocellular carcinoma (HCC) patients have been reported; however, their generalizability is unclear. Using two HCC patient datasets, we assessed the prognostic values of these gene signatures and identified 11 gene signatures that were associated with overall survival for postoperative HCC patients in both cohorts. Genes derived from these signatures formed a functional protein-protein interaction network with 1,406 nodes and 10,135 edges, and the expression levels of three core genes, RAD21, CDK1, and HDAC2, in the network were negatively associated with the overall survival of HCC patients. Further studies suggested that CDK1 is an independent prognostic factor and that it is a potential therapeutic target for HCC patients. Many molecular classification and prognostic gene signatures for hepatocellular carcinoma (HCC) patients have been established based on genome-wide gene expression profiling; however, their generalizability is unclear. Herein, we systematically assessed the prognostic effects of these gene signatures and identified valuable prognostic biomarkers by integrating these gene signatures. With two independent HCC datasets ( GSE14520 , N?=?242 and GSE54236 , N?=?78), 30 published gene signatures were evaluated, and 11 were significantly associated with the overall survival (OS) of postoperative HCC patients in both datasets. The random survival forest models suggested that the gene signatures were superior to clinical characteristics for predicting the prognosis of the patients. Based on the 11 gene signatures, a functional protein-protein interaction (PPI) network with 1406 nodes and 10,135 edges was established. With tissue microarrays of HCC patients (N?=?60), we determined the prognostic values of the core genes in the network and found that RAD21, CDK1, and HDAC2 expression levels were negatively associated with OS for HCC patients. The multivariate Cox regression analyses suggested that CDK1 was an independent prognostic factor, which was validated in an independent case cohort (N?=?78). In cellular models, inhibition of CDK1 by siRNA or a specific inhibitor, RO-3306, reduced cellular proliferation and viability for HCC cells. These results suggest that the prognostic predictive capacities of these gene signatures are reproducible and that CDK1 is a potential prognostic biomarker or therapeutic target for HCC patients.
机译：强调 ？十一种基因签名对于接受手术治疗的HCC患者的OS预测具有很有希望的价值。 ？ 11个基因签名的预测结果处于中等一致性，并且所包含的基因在功能上相关。 ？ CDK1是独立的预后生物标志物，是肝癌患者的潜在治疗靶标。已经报道了肝细胞癌（HCC）患者的各种基因特征。但是，它们的普遍性尚不清楚。我们使用两个HCC患者数据集，评估了这些基因特征的预后价值，并确定了与这两个队列中HCC患者术后总体生存率相关的11个基因特征。从这些签名中获得的基因形成了一个功能性的蛋白质-蛋白质相互作用网络，具有1,406个节点和10,135个边缘，并且网络中三个核心基因RAD21，CDK1和HDAC2的表达水平与HCC患者的整体生存呈负相关。进一步的研究表明，CDK1是一个独立的预后因素，它是肝癌患者的潜在治疗靶标。基于全基因组基因表达谱分析，已经建立了许多肝细胞癌（HCC）患者的分子分类和预后基因标记。但是，它们的普遍性尚不清楚。在本文中，我们系统地评估了这些基因签名的预后效果，并通过整合这些基因签名确定了有价值的预后生物标志物。通过两个独立的HCC数据集（GSE14520，N == 242和GSE54236，N == 78），评估了30个已发布的基因签名，在这两个数据集中，有11个与术后HCC患者的总体生存（OS）显着相关。随机生存森林模型表明，基因特征优于临床特征，可预测患者的预后。基于11个基因签名，建立了具有1406个节点和10,135个边缘的功能性蛋白质-蛋白质相互作用（PPI）网络。使用肝癌患者的组织芯片（N≥60），我们确定了网络中核心基因的预后价值，并发现RAD21，CDK1和HDAC2表达水平与肝癌患者的OS呈负相关。多因素Cox回归分析表明CDK1是一个独立的预后因素，在一个独立病例队列中得到了验证（N≥78）。在细胞模型中，siRNA或特异性抑制剂RO-3306对CDK1的抑制作用会降低HCC细胞的细胞增殖能力和活力。这些结果表明，这些基因签名的预后预测能力是可重现的，并且CDK1是HCC患者的潜在预后生物标志物或治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号