张林 欧祥琴 张涛 钟凯 吴学会 李睿思 李青璇 梁峰 张轩

摘要 目的：根據加权基因共表达网络（WGCNA）探索槲皮素抗胃癌的潜在生物靶标。方法：利用TCGA数据库下载胃癌相关转录组和临床数据，分析胃癌转录组表达的差异基因，利用网络药理学找到槲皮素的作用靶点，找出槲皮素与胃癌的hub基因。通过KEGG通路，GO基因富集分析寻找hub基因的靶点及通路，探索hub基因的在胃癌临床数据中的生存分析和性状表达的差异。结果：1）共发现槲皮素142个靶点，共139个蛋白质-蛋白质相互作用关系;2）KEGG通路富集分析发现槲皮素抗胃癌的作用通路可能与细胞衰老、MicroRNAs的表达、P53信号通路有关;3）生存分析发现纤溶酶原激活物抑制剂-1（SERPINE1）、微囊蛋白-1（Caveolin-1）、雄性激素受体（AR）、转录因子E2F2（E2F2）、前列腺素E2受体EP3亚型（PTGER3）在胃癌中的表达差异会影响患者的预后（P<0.05）;4）在胃癌的TNM分期中，AR与PTGER3的表达差异与胃癌的分期相关（P<0.05）;5）GEPIA数据库分析，AR与PTGER3在胃癌组织中的表达存在一定的相关性（P<0.05）。结论：槲皮素抗胃癌机制可能和细胞凋亡、MicroRNAs表达和P53信号通路有关，通过多靶点作用于SERPINE1、CAV1、AR、E2F2、PTGER3，发挥抑制癌细胞，改善患者预后的作用。

关键词 加权基因共表达网络;胃癌;hub基因;槲皮素

Study on the Mechanism of Quercetin Anti-gastric Cancer Gene Module and Molecular Marker Based on Weighted Gene Co-expression Network

ZHANG Lin1，OU Xiangqin2，ZHANG Tao3，ZHONG Kai3，WU Xuehui3，LI Ruisi3，LI Qingxuan3，LIANG Feng3，ZHANG Xuan4

（1 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China; 2 The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine，Guiyang 550001，China; 3 Tianjin University of Traditional Chinese Medicine，Tianjin 301608，China; 4 School of Chinese Medicine，Hong Kong Baptist University，Hong Kong 99077，China）

Abstract Objective：To explore the potential biological target of quercetin against gastric cancer based on the weighted gene co-expression network（WGCNA）.Methods：TCGA database was used to download gastric cancer related transcriptome and clinical data to analyze the differential genes expressed in gastric cancer transcriptome.Meanwhile，network pharmacological means was used to find the drug action targets of quercetin and find the hub genes of quercetin in gastric cancer.The targets and pathways of hub genes were searched through KEGG pathway and GO gene enrichment analysis which were aimed to explore the survival analysis and trait expression differences of hub genes in clinical data of gastric cancer.Results：1）A total of 142 targets and 139 protein interactions were found for quercetin.2）Enrichment analysis of KEGG pathway found that the anti-gastric cancer pathways of quercetin may be related to cell senescence，the expression of MicroRNAs，and the P53 signaling pathway.3）Survival analysis found that the expression differences of plasminogen activator inhibitor-1（SERPINE1），microencapsulated protein-1（Caveolin-1），androgen receptor（AR），transcription factor E2F2（E2F2），and prostagtin E2 receptor EP3 subtype（PTGER3）in gastric cancer affected the prognosis of patients（P<0.05）.4）In TNM staging of gastric cancer，the difference in expression of AR and PTGER3 was correlated with the staging of gastric cancer（P<0.05）.5）GEPIA database analysis showed that there was a certain correlation between AR and PTGER3 expression in gastric cancer tissues（P<0.05）.Conclusion：The anti-gastric cancer mechanism of quercetin may be related to apoptosis，MicroRNAs expression and P53 signaling pathway.It acts on SERPINE1，CAV1，AR，E2F2，and PTGER3 through multiple targets to inhibit cancer cells and improve the prognosis of patients.

Keywords Weighted gene co-expression network; Gastric cancer; Hub genes; Quercetin

中图分类号：R285文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.04.004

胃癌（Gastric Carcinoma，GC）是指源自胃黏膜上皮的恶性肿瘤，是全球发病率最高的5种肿瘤之一，在与癌症有关的死亡人数中排名第3位[1]。GC为全球医疗体系带来巨大的医疗和经济问题[2]。由于诊断和治疗方法的改进，早期GC患者生存率有所提高，但晚期GC的疗效不理想。而且由于GC的诊断往往被延迟，临床处理效率低，因此大多数GC病例诊断的时候已经表现为局部扩散或转移[3]。根据中华人民共和国国家卫生健康委员会发布的《2018胃癌诊疗规范》[4]，GC的治疗原则是多学科综合治疗，使用手术、化疗、放疗和生物靶向治疗等手段，此规范同时指出中医药治疗GC有助于改善手术并发症，缓解放化疗的不良反应，肯定了中医药治疗GC的疗效。……