基于生物信息基因表达谱的乳腺癌转移基因标志物的分析研究  

Genomic biomarker investigation for metastasis of breast cancer by combined bioinformatic gene expression profile analysis

作　　者：吴奇桥 张树民 郑婷婷 刘娟 胡永 林登强 戴梦婷 孙菁 WU Qiqiao;ZHANG Shumin;ZHENG Tingting;LIU Juan;HU Yong;LIN Dengqiang;DAI Mengting;SUN Jing(Department of Radiation Oncology,Fudan University Zhongshan Hospital(Xiamen Branch),Fujian Province,Xiamen361006,China;Department of Radiation Oncology,Fudan University Zhongshan Hospital,Shanghai200030,China;Department of Radiology,Fudan University Zhongshan Hospital(Xiamen Branch),Fujian Province,Xiamen361006,China;Department of Urological Surgery,Fudan University Zhongshan Hospital(Xiamen Branch),Fujian Province,Xiamen361006,China)

机构地区：[1]复旦大学附属中山医院厦门医院放疗科,福建厦门361006 [2]复旦大学附属中山医院放疗科,上海200030 [3]复旦大学附属中山医院厦门医院放射科,福建厦门361006 [4]复旦大学附属中山医院厦门医院泌尿外科,福建厦门361006

出　　处：《中国当代医药》2021年第36期22-28,共7页China Modern Medicine

摘　　要：目的确定潜在和乳腺癌转移相关的基因标志物,并对其进行生存分析。方法使用基因表达综合数据库(GEO),筛选乳腺癌转移部位和非转移部位之间的差异表达基因(DEGs)。对DEGs进行基因本体(GO)和京都基因与基因组百科全书途径富集(KEGG)分析,构建蛋白质-蛋白质交互(PPI)网络,并使用MCODE进行模块分析。然后,通过Kaplan-Meier工具对中枢基因进行总生存(OS)和远处无转移生存(DMFS)分析。通过GEPIA对基因和临床生存数据的相关性进行验证。结果本研究共获得295个DEGs,主要与细胞外分泌、粘着相关通路、细胞分裂相关。KEGG通路分析表明,重要的通路包括丝裂原活化蛋白激酶(MAPK)信号通路、Rap1信号通路、细胞粘附分子(CAMs)、抗原加工和呈递。建立了具有280个节点和357个连接的蛋白-蛋白交互网络。从蛋白-蛋白交互网络中发现了10个模块。结论共筛选出20个基因作为枢纽基因,其中TYMS、SKA1、ADCY7的低表达和MX1的高表达与OS较差有关。POLR3H的低表达和CDCA8、ASE1、KIF14、MX1的高表达与较差的DMFS有关。POLR3H和PRC1可作为诊断乳腺癌转移或潜在药物靶标的新生物标志物。Objective To identify potential genetic markers associated with breast cancer metastasis and to perform survival analysis.Methods The comprehensive Gene Expression Omnibus(GEO)was used to screen differentially expressed genes(DEGs)between metastatic and non-metastatic sites of breast cancer.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were performed,the protein-protein interaction(PPI)network was constructed,and module analysis was performed using MCODE.Then,overall survival(OS)and distant metastasis free survival(DMFS)analysis of hub genes was performed by the Kaplan-Meier plotter online tool.The correlations between hub genes and clinical stages were validated through GEPIA online tool.Results A total of 295 DEGs were obtained,which were significantly enriched in the terms related to extracellular exosome,focal adhesion,cell division.KEGG pathway analysis showed that the significant pathways included mitogen-activated protein kinase(MAPK)signaling pathway,Rap1 signaling pathway,cell adhesion molecules(CAMs),antigen processing and presentation.The PPI network was established with 280 nodes and 357 edges.Ten modules were found from the PPI network.Conclusion A total of 20 genes were selected as hub genes,among which,low expression of TYMS,SKA1,ADCY7 and high expression of MX1 were related with worse overall survival.Low expression of POLR3H and high expression of CDCA8,ASE1,KIF14,MX1 were associated with worse DMFS.POLR3H and PRC1 may serve as new biomarker in diagnosing metastasis of breast cancer or potential drug target.

关 键 词：乳腺癌 转移 生物信息学分析 差异表达的基因 治疗药物 生存分析 

分 类 号：R735.2[医药卫生—肿瘤]