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作 者:刘婧婷 隆建萍[2] 金凤玲[1,3] 林碧玉 王文第[4] 裴建赢 王晶晶 Liu Jingting;Long Jianping;Jin Fengling(The First Clinical Medical College,The First Hospital Lanzhou University Lanzhou 730000,China;Department of Breast Surgery,Gansu Provincial Maternity and Child-care Hospital,Lanzhou 730050,China;Department of Hospital Infection Control,The First Hospital Lanzhou University Lanzhou 730000,China;Department of Breast Surgery,Maternal and Child Health Care Research Center,Gansu Provincial Maternity and Child-care Hospital,Lanzhou 730050,China)
机构地区:[1]兰州大学第一临床学院,兰州730000 [2]甘肃省妇幼保健院乳腺一科,兰州730050 [3]兰州大学第一医院感染管理科,兰州730000 [4]甘肃省妇幼保健院妇幼保健科研中心,兰州730050
出 处:《华中科技大学学报(医学版)》2022年第2期172-179,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基 金:甘肃省自然科学基金资助项目(No.17JR5RA030)。
摘 要:目的利用生物信息学方法研究细胞分裂周期相关蛋白(CDCAs)介导乳腺癌的潜在靶向基因、信号传导通路及分子机制。方法从GEO和TCGA数据库下载正常乳腺组织和乳腺癌样本的基因芯片;使用R软件limma包分析正常乳腺组织和乳腺癌样本之间的差异表达基因;使用Kaplan-Meier Plotter评估乳腺癌患者的整体生存率、无复发生存率和无远处转移生存率;对筛选出的差异表达基因进行GO和KEGG信号通路富集分析。结果通过对差异表达基因的趋势分析,筛选出2015个显著上调的基因以及864个显著下调的基因,其中CDCA1/2/3/5/7/8可能为介导乳腺癌浸润性进展的相关基因。生存分析表明,乳腺癌CDCA1/2/3/5/7/8高表达与不良预后相关(均P<0.05)。GO分析结果主要富集于细胞有丝分裂周期、染色姐妹单体分离、染色体、着丝粒、纺锤体等;KEGG信号通路富集分析则在卵母细胞减数分裂、p53信号通路、DNA复制显著富集。结论整合生物信息学分析结果,表明CDCAs在乳腺癌组织中表达升高,并且CDCAs表达水平显著影响乳腺癌患者预后,与其他CDCAs相比,CDCA2/3/5/8可能是乳腺癌患者靶向治疗的合适靶点。Objective To explore the potential target genes of cell division cycle-associated protein(CDCAs),signal transduction pathways and molecular mechanisms of breast cancer using bioinformatics technique.Methods Gene expression information including samples from normal mammary gland and breast cancer tissue were downloaded from GEO and TCGA database.The differentially expressed genes between normal tissues and breast cancer tissues were analyzed by limma package from R language.Kaplan-Meier Plotter was used to evaluate the overall survival rate,recurrent-free survival rate and distant metastasis-free survival rate of breast cancer patients.GO enrichment analysis and KEGG pathway analysis were performed on differentially expressed genes and predicted target genes,respectively.Results According to analysis of the differentially expressed genes,2015 up-regulated genes and 864 down-regulated genes were screened out in breast cancer tissue.The mRNA levels of CDCA1/2/3/5/7/8 might be correlated with the infiltration progression of breast cancer.Kaplan-Meier Plotter showed that high transcription levels of CDCA1/2/3/5/7/8 had good diagnostic efficacy for patients with breast cancer.GO analysis showed that the enrichment analysis was mainly involved in cell division,mitotic sister chromatid segregation,chromosome,kinetochore,spindle and so on.KEGG analysis showed significant enrichment in oocyte meiosis,p53 signaling pathway and DNA replication.Conclusion The integrative bioinformatics analysis performed in the present study suggestes that the expression of CDCAs increases in breast cancer.The high expression of some CDCAs have significant influence on the prognosis of patients with breast cancer.Compared with other CDCAs,CDCA2/3/5/8 are potentially appropriate targets for targeted therapy in patients with breast cancer.
关 键 词:乳腺癌 细胞分裂周期相关蛋白 生物信息学
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