徐信　薛晓鸥　宗春晓　王谦　邵晨曦　范梦腾　谢伟

〔摘要〕 目的 采用网络药理学联合GEO数据库差异基因分析的方法，探讨金雀异黄素（genistein）治疗子宫内膜癌（endometrial carcinoma， EC）的潜在作用机制。方法 依托TCMSP等8个数据库获得金雀异黄素的靶标基因，并通过Uniport蛋白质数据库进行名称规范;然后，运用GEO数据库获取子宫内膜癌GSE17025数据集，并运用R语言获取其差异表达的基因;进而，作金雀异黄素靶标基因与子宫内膜癌差异基因的映射集合，再将交集靶点提交至STRING平台获得蛋白互作网络，并采用Cytoscape 3.7.2进行网络拓扑分析，筛选重要靶点;最后，对交集靶点进行GO注释和KEGG富集分析。结果 金雀异黄素作用于70个交集靶点发挥对子宫内膜癌的治疗作用，其中重要靶点有STAT3、BIRC5、MKI67等基因，主要富集在IL-17（IL-17 signaling pathways）、p53（p53 signaling pathway）、TGF-β（TGF-beta signaling pathway）等多条信号通路上。结论 金雀异黄素通过多靶点、多途径治疗子宫内膜癌，其可能是通过IL-17、p53、TGF-β等信号通路发挥治疗作用。此研究为深入阐释金雀异黄素治疗子宫内膜癌的临床研究及进一步实验验证提供了思路。

〔关键词〕 金雀异黄素;子宫内膜癌;网络药理学;分子作用机制;GEO芯片

〔中圖分类号〕R285       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.12.022

〔Abstract〕 Objective To explore the potential mechanism of genistein in the treatment of endometrial carcinoma （EC） by network pharmacology and differentially expressed genes （DEGs） of GEO chip. Methods The TCMSP database and other 7 databases were used to obtain the target genes of genistein， and the target protein name was transformed into the target gene name by the Uniport protein database; the GEO chip was used to obtain the EC GSE17025 data set， and the R language was used to obtain its differentially expressed genes; furthermore， the mapping collection of genistein target genes and EC differential genes was made， and then the intersection targets were submitted to the STRING platform to obtain the protein interaction network. The Cytoscape 3.7.2 was used to perform network topology analysis to screen important targets; finally， GO annotation and KEGG enrichment analysis were performed on the intersection target. Results Genisteine acted on 70 intersection targets to play a therapeutic role on EC. Among them， STAT3， BIRC5 and MKI67 and other genes were important targets， which were enriched in IL-17 signaling pathways， p53 signaling pathway and TGF-β signaling pathway. Conclusion Genistein can treat EC by multi-target and multi-channel， which may play a therapeutical effect through IL-17， p53， TGF-β and other signal pathways. This study provides an idea for in-depth explanation of the clinical research and further experimental verification of genistein in the treatment of EC.

〔Keywords〕 genistein; endometrial carcinoma; network pharmacology; molecular mechanism; GEO chip

子宫内膜癌（endometrial carcinoma， EC），又称子宫体癌，是来源于子宫内膜的上皮性恶性肿瘤[1]。据美国癌症协会2019年公布的最新数据，子宫内膜癌发病率仍高居女性生殖系统恶性肿瘤第一位[2]，发病率呈上升态势，年龄日趋年轻化，死亡率也呈逐步上升趋势[3]，手术治疗仍是其治疗的主要手段，然而，术后复发率高，同时也严重破坏了妇女的生育力[4]。……