A comparative study of cancer proteins in the human protein-protein interaction network.
A comparative study of cancer proteins in the human protein-protein interaction network.
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DOI：
10.1186/1471-2164-11-s3-s5
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发表时间：
2010-12-01
期刊：
影响因子：
4.4
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Sun J;Zhao Z
癌症是一种复杂的疾病。到目前为止，已经报道了许多基因与癌症的发展有关。与研究单个基因或基因座的传统方法不同，对人类蛋白质-蛋白质相互作用网络中癌症蛋白的系统研究可能为揭示癌症和其他潜在复杂疾病的分子机制提供重要的生物学信息。我们探索了人类相互作用组中由癌症基因（癌蛋白）编码的蛋白质的全局和局部网络特征。我们发现癌症蛋白的网络拓扑结构与必需基因（必需蛋白）或控制基因（控制蛋白）编码的蛋白质有很大的不同。相对于必需蛋白或控制蛋白，肿瘤蛋白在人类相互作用组中的程度更高、中间度更高、最短路径距离更短、聚类系数更弱。我们进一步将肿瘤蛋白分为两组（隐性和显性肿瘤蛋白），并比较了它们的拓扑特征。隐性癌蛋白比显性癌蛋白具有更高的中间性，但其程度分布和特征最短路径距离也存在显著差异。最后，我们发现癌症蛋白在人类相互作用组中并不是随机分布的，它们之间的联系很强。我们的研究表明，相对于整个人类相互作用组中的必需蛋白或控制蛋白，癌症蛋白具有更强的蛋白质-蛋白质相互作用特征。我们还发现隐性癌蛋白的网络特征比显性癌蛋白强。这些结果有助于癌症候选基因的优先排序和验证，生物标志物的发现，并最终在系统生物学水平上理解癌症的病因。
Cancer is a complex disease. So far, many genes have been reported to involve in the development of cancer. Rather than the traditional approach to studying individual genes or loci, a systematic investigation of cancer proteins in the human protein-protein interaction network may provide important biological information for uncovering the molecular mechanisms of cancer and, potentially, other complex diseases. We explored global and local network characteristics of the proteins encoded by cancer genes (cancer proteins) in the human interactome. We found that the network topology of the cancer proteins was much different from that of the proteins encoded by essential genes (essential proteins) or control genes (control proteins). Relative to the essential proteins or control proteins, cancer proteins tended to have higher degree, higher betweenness, shorter shortest-path distance, and weaker clustering coefficient in the human interactome. We further separated the cancer proteins into two groups (recessive and dominant cancer proteins) and compared their topological features. Recessive cancer proteins had higher betweenness than dominant cancer proteins, while their degree distribution and characteristic shortest path distance were also significantly different. Finally, we found that cancer proteins were not randomly distributed in the human interactome and they connected strongly with each other. Our study revealed much stronger protein-protein interaction characteristics of cancer proteins relative to the essential proteins or control proteins in the whole human interactome. We also found stronger network characteristics of recessive than dominant cancer proteins. The results are helpful for cancer candidate gene prioritization and verification, biomarker discovery, and, ultimately, understanding the etiology of cancer at the systems biological level.