E2F转录因子家族在宫颈癌中的表达及其与临床预后的关系  

The expression for E2Fs in human cervical cancer and its relationship with clinical prognosis

作　　者：陈玥 佘婧瑶 陈思[1] 曹莹 梁春云[1,2] 卢燕 王佩娟[1] 公真[1] CHEN Yue;SHE Jingyao;CHEN Si;Cao Ying;LIANG Chunyun;LU Yan;WANG Peijuan;Gong Zhen(Department of Obstetrics and Gynecology,Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing 210028,China;The Third Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]江苏省中西医结合医院妇产科,江苏南京210028 [2]南京中医药大学第三临床医学院,江苏南京210023

出　　处：《山东第一医科大学（山东省医学科学院）学报》2023年第3期215-223,共9页Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences

基　　金：国家自然科学基金青年项目(81903998);国家自然科学基金面上项目(82074487)。

摘　　要：目的 研究E2F家族在宫颈癌中的表达、预后价值以及与免疫浸润之间的关系。方法 采用Oncomine数据库分析E2F转录因子家族在不同类型癌症中的表达差异。采用GEPIA 2数据库分析E2F转录因子家族在宫颈癌组织与正常组织中的表达及不同临床分期间的差异。采用Kaplan-Meier plotter数据库分析E2F转录因子家族在宫颈癌中的预后价值。使用cBioPortal数据库进行E2F转录因子家族的共表达基因和遗传学突变分析。采用WebGestalt数据库对E2F家族相关基因进行功能及通路的富集分析。采用TIMER 2.0数据库分析E2F转录因子家族与宫颈癌中免疫细胞浸润的相关性。结果 宫颈癌中E2F1、E2F2、E2F3、E2F7、E2F8的表达均较正常宫颈组织高,但与临床分期无明显相关性。预后分析显示,E2F1高表达和E2F3低表达与患者更长的总生存期(overall survival,OS)和无复发生存期(recurrence free survival,RFS)明显相关。基因变异分析显示,E2F1基因变异率为5%,为E2F家族中最高。计算宫颈癌E2F家族成员之间的相关性结果表明,E2F2与E2F7、E2F8的表达,E2F3与E2F5的表达,E2F7与E2F8的表达均呈正相关;E2F2与E2F5的表达呈负相关。GO分析显示,E2F基因家族的相关功能主要指向生物调节和能量代谢;KEGG分析显示,E2F基因家族主要与细胞分裂、衰老及细胞周期密切相关。TIMER2.0数据库分析显示,部分E2F家族成员的表达水平与CD4^(+)T细胞、CD8^(+)T细胞浸润呈正相关,与巨噬细胞浸润呈负相关。结论 E2F转录因子家族在宫颈癌中存在表达失调,家族成员E2F1,2,3,7,8是未来宫颈癌精准治疗的潜在靶点,而E2F1和E2F3可能成为评价宫颈癌预后新的生物标志物。Objective:To explore the expression profiles and prognostic value of E2F family members and their relations with immune infiltration and relevant functions based on bioinformatics approaches.Methods:The expression of E2F family members in different cancer types were analyzed using Oncomine database,and their expression levels in different cervical cancer clinical stages were evaluated using GEPIA 2 database.Then the prognostic value of E2Fs expression in cervical cancer was assessed using Kaplan-Meier plotter database.The co-expression profiles and genetic alterations of E2F family members were analyzed using the cBioPortal.The function and pathway enrichment analysis of E2F family were performed using WebGestalt database and the correlation analysis of E2F family and immune cell infiltration in cervical cancer was conducted using TIMER 2.0 database.Results:The mRNA expression levels of E2F1,E2F2,E2F3,E2F7 and E2F8 in cervical cancer were significantly increased compared with those in normal cervical tissues,but showed no significant correlations with tumor stage.Prognostic analysis showed that high expressions of E2F1 and low expressions of E2F3 were significantly associated with longer overall survival(OS)and relapse-free survival(RFS).Analysis of the TCGA database and cBioPortal showed that the genetic alteration rate of E2F1 was 5%,which was the highest among E2F family members.GO function enrichment analysis showed that the main functions of E2F family were oriented toward the biological processes regulation and energy metabolism.KEGG pathway enrichment analysis showed that the main functions of E2Fs were related to cell division,cell cycle and cellular senescence.The TIMER 2.0 database analysis showed that the expressions of most E2F family members were significantly positively correlated with the infiltration of CD4+T cells,and negatively correlated with the infiltration of CD8+T cells and macrophages.Conclusion:The molecular and expression profiles of E2Fs members are dysregulated in cervical cancer,and E

关 键 词：宫颈癌 E2F转录因子家族 预后 免疫细胞浸润 生物信息学 

分 类 号：R737.33[医药卫生—肿瘤]