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目的滑膜肉瘤(synovial sarcoma,SS)是一种来源不明的软组织恶性肿瘤,临床上较少见。随着分子生物学的不断发展,从分子层面了解滑膜肉瘤并发现其相关生物学通路,以此寻找其治疗靶点成为目前研究的热点。本研究通过建立蛋白质相互作用网络预测滑膜肉瘤的生物学通路,以期发现其相关作用靶点。方法通过在线人类孟德尔遗传数据库筛选出滑膜肉瘤相关基因,采用Cytoscape软件和插件Agilent Literature Search进行文本挖掘并建立滑膜肉瘤的蛋白质相互作用网络;采用插件Clusterviz,发现网络中可能包含的分子复合物;基于DAVID富集分子复合物的生物学通路。结果通过人类孟德尔遗传数据库筛选出滑膜肉瘤相关基因有67个;采用Cytoscape软件挖掘出滑膜肉瘤相关蛋白质相互作用网络包含489个节点(蛋白质)和1 414条边(相互作用关系);Clusterviz插件发现其可能包含6个分子复合物;通过DAVID对这6个分子复合物进行富集,获得其相关生物学通路,以错误发现率(false discovery rate,FDR)<1为差异有统计学意义,最终获得分子复合物1有7条通路,分子复合物2有45条通路。分子复合物3、4、5和6的细胞通路FDR值均>1,差异无统计学意义。结论分子复合物1主要与p53信号通路及细胞因子调节有关,且与膀胱癌有相关性;分子复合物2涉及通路较多,说明滑膜肉瘤的发生是一个受多种细胞通路、多基因构成的网络协同调控的复杂过程。
ObjectiveSynovial sarcoma (SS) is an unknown source of soft tissue malignant tumors, clinically rare. With the continuous development of molecular biology, understanding synovial sarcoma at the molecular level and finding its related biological pathways, in order to find its therapeutic target has become a hot research field. In this study, we established a protein-protein interaction network to predict the biological pathway of synovial sarcoma, in order to find its relevant target. Methods The related genes of synovial sarcoma were screened from the on-line human Mendelian genetic database. The Cytoscape software and the plug-in Agilent Literature Search were used for text mining and the protein-protein interaction network of synovial sarcoma was established. Clusterviz was used to discover the molecular complex Biological pathway based on DAVID enriches molecular complexes. Results 67 human synovial sarcoma-related genes were screened from the Mendelian genetic database. Cytoscape software was used to discover the related protein-protein interaction networks of synovial sarcoma including 489 nodes (protein) and 1 414 edges (interaction); Clusterviz The plugin found that it may contain six molecular complexes; these six molecular complexes were enriched by DAVID and their related biological pathways were obtained, with a statistically significant difference of false discovery rate (FDR) <1 Finally, the molecular complex 1 has 7 channels and the molecular complex 2 has 45 channels. The FDR values of cell complexes in molecular complexes 3, 4, 5, and 6 were all> 1, with no significant difference. Conclusions Molecular complex 1 is mainly involved in the regulation of p53 signaling pathway and cytokines, and has a correlation with bladder cancer. Molecular complex 2 involves more pathways, indicating that the occurrence of synovial sarcoma is a multi-cellular pathway with multiple genes The complex process of network coordination and control.