摘要
目的通过生物信息学方法筛选影响宫颈癌辐射敏感性的差异基因并进行表达验证以及免疫相关性分析。方法从GEO数据库下载包含放疗前后宫颈癌组织、正常宫颈组织、宫颈癌组织的数据集,使用R软件筛选其中的差异基因,使用韦恩图取交集筛选宫颈癌辐射敏感性差异基因。从TCGA数据库及GTEx数据库收集宫颈癌组织样本、正常宫颈组织样本的表达数据及患者临床资料、随访数据,通过GEPIA2数据库对筛选出的宫颈癌辐射敏感性差异基因进行表达分析,验证所选差异基因是否可靠。通过GEPIA2数据库进行生存分析,筛选不同基因表达水平对患者预后有影响的差异基因为宫颈癌辐射敏感性关键差异基因;通过R软件对患者临床资料及预后情况进行单因素、多因素COX回归分析,验证筛选出的关键差异基因是否为宫颈癌患者预后的影响因素;通过HPA数据库比较筛选出的关键差异基因在宫颈癌以及正常宫颈组织中的蛋白表达。通过基因集富集分析对关键差异基因的GO功能及KEGG信号通路进行富集分析,通过TIMER数据库分析关键差异基因在宫颈癌中的表达与免疫细胞浸润水平的关系,通过TCGA数据库数据观察免疫检查点相关基因的表达情况,并对关键差异基因与宫颈癌高度相关的免疫检查点基因进行Spearman相关性分析。结果共筛选出宫颈癌辐射敏感性差异基因10个,分别为HELLS、TOP2A、KIF23、TAP1、WDR76、LMNB1、RFC4、TFRC、IFI44L、IFIT3;10个差异基因均在宫颈癌组织中高表达。生存分析结果显示,TFRC高表达的宫颈癌患者总生存率及无病生存率低于TFRC低表达的患者,故选择TFRC为宫颈癌辐射敏感性关键差异基因。单因素COX回归分析结果显示,TFRC及宫颈癌TNM分期是宫颈癌患者预后的影响因素;多因素COX回归分析结果显示,TFRC及宫颈癌TNM分期是宫颈癌患者预后的独立影响因素。通过HPA数据�
Objective To screen the differentially expressed genes(DEGs)affecting radiosensitivity of cervical can⁃cer and to conduct the expression validation and immune correlation analysis by bioinformatics methods.Methods The datasets of cervical cancer tissues before or after radiotherapy,normal cervical tissues and cervical cancer tissues were downloaded from Gene Expression Database(GEO),and the DEGs of cervical cancer were screened by Rstudio software,and Venn diagram was used to screen DEGs for radiosensitivity of cervical cancer.The expression data of cervical cancer tissue samples and normal cervical tissue samples,and clinical information and follow-up data of the patients were collect⁃ed from TCGA database and GTEx database.DEGs for radiosensitivity of cervical cancer were screened and their expres⁃sion levels were analyzed from GEPIA2 database,and then the reliability of selected DEGs were verified.The key DEGs for radiosensitivity of cervical cancer were screened through the effects of different gene expression levels on patients'prog⁃nosis by survival analyses from GEPIA2 database.The clinical data and prognosis of patients were porformed by single fac⁃tor and multi-factor COX regression analyses to verify the screened key DEGs as the influencing factors on the prognosis of cervical cancer patients by Rstudio software.The protein expression of screened key DEGs between cervical cancer and normal cervical tissues was compared through HPA database.The gene enrichment analysis was set for GO function and KEGG signaling pathways of key DEGs.The relationship between the expression of key DEGs in cervical cancer and the in⁃filtration level of immune cells was analyzed through TIMER database.The expression of immune checkpoint-related genes were observed through TCGA database.Spearman correlation analysis was conducted on the key DEGs and immune check⁃point genes highly associated with cervical cancer.Results Ten DEGs with cervical cancer radiosensitivity were screened out,which were HELLS,TOP2A,KIF23,
作者
胡煜
王含梦
陈然众
彭昌民
李乐
唐双阳
HU Yu;WANG Hanmeng;CHEN Ranzhong;PENG Changmin;LI Le;TANG Shuangyang(School of Public Health,University of South China,Hengyang 421001,China;不详)
出处
《山东医药》
CAS
2023年第29期20-24,共5页
Shandong Medical Journal
基金
国家自然科学基金项目(81402169)
湖南省自然科学基金项目(202150014)
湖南省卫生健康委科研重点项目(202105012137)
衡阳市科技计划项目(202002042122)。
关键词
辐射敏感
放射治疗
免疫治疗
免疫检测点
生物信息学
宫颈癌
radiosensitivity
radiotherapy
immunotherapy
immune checkpoint
bioinformatics
cervical carci⁃noma
