Wang P, Ouyang L, Zheng L, Wang Z
Department of General Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan, China.
Ir J Med Sci. 2015 Jun;184(2):357-64. doi: 10.1007/s11845-014-1119-y. Epub 2014 Apr 18.
Previous researches have been focused on revealing the functions of each individual gene and/or pathway in the initiation, progression and maintenance of hepatocellular carcinoma (HCC). However, the mechanistic relationships among different genes and/or pathways are largely unknown.
In this study, we tended to uncover the potential molecular networks and critical genes which play important roles in HCC progression.
The transcriptional profiles from normal and HCC patient samples were analyzed and compared using bioinformatic methods, including differentially expressed gene (DEG) analysis, hierarchical clustering, construction of protein-protein interaction (PPI) network and GO-Elite analysis.
Initially, the normal and HCC sample data were processed and 679 most dramatic DEGs were identified. The PPI network analysis indicates the significance of multiple biological processes as well as signaling pathways in affecting liver function and HCC progression. In addition, hierarchical clustering analysis showed the most significant modules and identified the relationship between different genes, and some important genes such as FOS, IGF1, ADH4, ITGA2 and LEF1 were found to be hubs which master each individual module.
Our study greatly improves the understanding of the HCC development in a systematic manner and provides the potential clue for exploiting drugs which might target the most significant genes and/or signaling pathways.
以往的研究主要集中在揭示各个基因和/或信号通路在肝细胞癌(HCC)的发生、发展和维持过程中的功能。然而,不同基因和/或信号通路之间的机制关系在很大程度上尚不清楚。
在本研究中,我们试图揭示在HCC进展中起重要作用的潜在分子网络和关键基因。
使用生物信息学方法分析和比较正常和HCC患者样本的转录谱,包括差异表达基因(DEG)分析、层次聚类、蛋白质-蛋白质相互作用(PPI)网络构建和GO-Elite分析。
首先,对正常和HCC样本数据进行处理,鉴定出679个差异最为显著的DEG。PPI网络分析表明多个生物学过程以及信号通路在影响肝功能和HCC进展方面的重要性。此外,层次聚类分析显示了最显著的模块,确定了不同基因之间的关系,并发现一些重要基因如FOS、IGF1、ADH4、ITGA2和LEF1是主导各个模块的枢纽基因。
我们的研究极大地提高了对HCC发生发展的系统认识,并为开发可能靶向最重要基因和/或信号通路的药物提供了潜在线索。