摘要
目的从拷贝数异常(copy number variations,CNVs)的角度出发,探讨细胞周期相关基因在高级别浆液性卵巢癌(high-grade serous ovarian cancer,HGSOC)发生及发展中的作用。方法从GEO、TCGA、GO、KEGG、REACTOME、BIOCARTA等数据库中筛选出HGSOC患者的CNVs及差异表达基因(differentially expressed genes,DEG),将这些基因与细胞周期相关基因进行整合,对这些被整合的基因进行相关预后分析。结果整合3213个与HGSOC细胞周期相关的基因、2046个CNVs基因和1777个DEG,确定36个与HGSOC细胞周期相关、同时发生CNVs和差异表达的共突变基因,这些共突变基因均来自拷贝数扩增组。基因关联性分析发现:MECOM和PRKCI、PRKCI和ECT2的共表达概率较大,分别约为32.5%、30.1%。结合生存曲线发现:ECT2、RAD51AP1、YWHAZ、RAD21、SMC4、TFB2M等6个基因与HGSOC的无进展生存率(progression-free survival,PFS)和总体生存率(overall survival,OS)显著相关(HR>1,P<0.05),这些基因高表达的HGSOC患者其PFS及OS大幅下降(P<0.05)。结论HGSOC的发生其原因可能是因为拷贝数扩增导致DEG的上调,从而影响细胞周期;MECOM、PRKCI、ECT2可能共用了某条信号通路,而在该通路的作用下可加速HGSOC的发生发展;ECT2、RAD51AP1、YWHAZ、RAD21、SMC4、TFB2M作为HGSOC不良生存预后基因,在该疾病发生发展中起着重要的作用,可作为HGSOC药物治疗的潜在靶点。
Objective To investigate the role of cell cycle-related genes in occurrence and development of high-grade serous ovarian cancer(HGSOC)from the perspective of copy number variations(CNVs).Methods The CNVs and differentially expressed genes(DEGs)were screened out from the databases of GEO,TCGA,GO,KEGG,REACTOME and BIOCARTA.The genes were integrated with cell cycle-related genes to analyze the prognosis.Results A total of 36 co-expressed genes from copy number amplification group were selected by integrating 3213 cell cycle-related genes,2046 genes with cell cycle-related genes and 1777 DEGs.Association analysis of genes showed a high probability of co-expression of MECOM and PRKCI(32.5%),as well as PRKCI and ECT2(30.1%).Survival curve revealed that ECT2,RAD51AP1,YWHAZ,RAD21,SMC4 and TFB2M were significantly correlated with the progression-free survival(PFS)and overall survival(OS)(HR>1,P<0.05).Furthermore,both PFS and OS dramatically decreased in HGSOC patients with high expression of these genes(P<0.05).Conclusion The occurrence of HGSOC may be due to the up-regulation of DEGs caused by copy number amplification,which affects the cell cycle.MECOM,PRKCI and ECT2 may share a signal pathway,which promotes the occurrence and development of HGSOC.As the poor survival and prognosis genes,ECT2,RAD51AP1,YWHAZ,RAD21,SMC4 and TBF2M play important role in the occurrence and development of HGSOC,and therefore can be used as the potential targets for therapy of HGSOC.
作者
周潇妮
付振华
张琦玲
陈敏杰
蔡丽萍
ZHOU Xiao-ni;FU Zhen-hua;ZHANG Qi-ling;CHEN Min-jie;CAI Li-ping(Medical Department of Graduate School,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Queen Mary College,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Department of Obstetrics and Gynecology,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China)
出处
《南昌大学学报（医学版）》
CAS
2020年第3期19-25,共7页
Journal of Nanchang University：Medical Sciences
基金
江西省自然科学基金(20192ACBL20038,20152ACG70022)。
关键词
高级别浆液性卵巢癌
细胞周期相关基因
拷贝数变异
差异表达基因
high-grade serous ovarian cancer
cell cycle-related genes
copy number variations
differentially expressed genes
