Cai Yu-Dong, Zhang Qing, Zhang Yu-Hang, Chen Lei, Huang Tao
School of Life Sciences, Shanghai University , Shanghai 200444 People's Republic of China.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, People's Republic of China.
J Proteome Res. 2017 Feb 3;16(2):1027-1038. doi: 10.1021/acs.jproteome.6b00950. Epub 2017 Jan 23.
Tumor metastasis is defined as the spread of tumor cells from one organ or part to another that is not directly connected to it, which significantly contributes to the progression and aggravation of tumorigenesis. Because it always involves multiple organs, the metastatic process is difficult to study in its entirety. Complete identification of the genes related to this process is an alternative way to study metastasis. In this study, we developed a computational method to identify such genes. To test our method, we selected breast cancer bone metastasis. A large network was constructed using human protein-protein interactions. On the basis of the validated genes related to breast and bone cancer, a shortest path algorithm was applied to the network to search for novel genes that may mediate breast cancer metastasis to bone. In addition, further rules constructed using the permutation FDR, the betweenness ratio, and the max-min interaction score were also employed in the method to make the inferred genes more reliable. Eighteen putative genes were identified by the method and were extensively analyzed. The confirmation results indicate that these genes participate in metastasis.
肿瘤转移被定义为肿瘤细胞从一个器官或部位扩散到与其没有直接连接的另一个器官或部位，这显著促进了肿瘤发生的进展和恶化。由于肿瘤转移总是涉及多个器官，因此很难对整个转移过程进行研究。完全鉴定与该过程相关的基因是研究转移的另一种方法。在本研究中，我们开发了一种计算方法来鉴定此类基因。为了测试我们的方法，我们选择了乳腺癌骨转移。利用人类蛋白质-蛋白质相互作用构建了一个大型网络。基于与乳腺癌和骨癌相关的已验证基因，将最短路径算法应用于该网络，以寻找可能介导乳腺癌转移至骨的新基因。此外，该方法还使用了基于置换错误发现率、中介中心性比率和最大-最小相互作用得分构建的进一步规则，以使推断出的基因更可靠。通过该方法鉴定出了18个假定基因，并对其进行了广泛分析。确认结果表明这些基因参与了转移过程。
