Liu G, Li D Z, Jiang C S, Wang W
Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou, China.
Braz J Med Biol Res. 2014 May;47(5):369-75. doi: 10.1590/1414-431x20143527.
To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.
为研究胃癌的信号调控模型，利用数据库和文献构建人类信号网络。通过CytoScape分析网络的拓扑特征。在标记从CancerResource、GeneRIF和COSMIC数据库中提取的胃癌相关基因后，使用FANMOD软件在具有三个顶点的网络中挖掘胃癌相关基序。采用显著基序差异法识别正常和癌症状态下显著不同的基序。最后，我们对显著不同的基序进行了一系列分析，包括基因本体、基因功能注释和模型分类。构建了一个人类信号网络，有1643个节点和5089个调控相互作用。该网络具有其他生物网络的特征。在总共69492个基序中，有57942个标记有胃癌相关基因，通过计算显著基序差异（SMD）分数，选择了264个基序作为显著不同的基序。显著不同基序中的基因主要富集于与癌症发生相关的功能，如细胞死亡调控、蛋白质氨基酸磷酸化和细胞内信号级联反应。前五个显著不同的基序主要是级联和正反馈类型。这五个基序中的几乎所有基因都与癌症相关，包括EPOR、MAPK14、BCL2L1、KRT18、PTPN6、CASP3、TGFBR2、AR和CASP7。抑制所选基序上下游的信号转导可能会抑制癌症的发展。
