摘要
目的探寻影响食管鳞状细胞癌放射敏感性及预后的关键基因,从基因组学水平揭示食管鳞状细胞癌放射治疗差异的相关因素。方法从基因芯片公共数据库Gene Expression Omnibus(GEO)中下载食管鳞癌接受放射治疗的相关芯片数据(GSE45670),采用limma程序包鉴定放射治疗病理学完全反应(pathological complete response,pCR)组和无反应(not pathological complete response,npCR)组基因的差异倍数,利用GSEA分析技术筛选并富集放射敏感性相关基因。从The Cancer Genome Atlas(TCGA)数据库中下载食管鳞癌的基因表达谱数据和临床资料,采用edgeR程序包鉴定肿瘤组织和正常组织间的差异基因。综合分析2个数据库,利用STRING数据库构建蛋白互作网络,并基于核心基因表达水平的高低分析患者的预后数据。结果GSEA表明GSE45670中放射治疗pCR和npCR组基因主要在细胞周期、DNA复制等生物学特征差异具有统计学意义(名义P值<0.05且错误发现率FDR<0.25),共鉴定出70个放射敏感性相关基因;edgeR分析,TCGA中食管鳞癌与正常组织间共筛选出4855个差异基因。综合两者及STRING数据库,共有46个基因与食管鳞癌发生及放射敏感性均相关,可以作为候选基因。进一步生存分析表明,PRIM1、PRKDC在肿瘤组织中和pCR组均高表达,且预后较好(P<0.05)。结论综合GEO和TCGA数据库,46个基因与食管鳞癌的发生及放射敏感性有关,26个基因可为核心基因,其中PRKDC、PRIM1在pCR组高表达且与预后良好相关。
Objective To explore the key genes affecting the radiosensitivity and prognosis of esophageal squamous cell carcinoma and reveal the related factors of radiotherapy differences in esophageal squamous cell carcinoma at the genomic level.Methods We downloaded the related chip data of esophageal squamous cell carcinoma receiving radiation therapy from the gene chip public database Gene Expression Omnibus(GEO)(GSE45670).The limma package was used to identify the differential folds of the genes in the pCR and npCR groups,and the genes related to radiosensitivity were screened and enriched using GSEA analysis.The gene expression profile data and clinical data of esophageal squamous cell carcinoma were downloaded from The Cancer Genome Atlas(TCGA)database,and the difference genes between tumor tissue and normal tissue were identified using the edgeR package.We made a comprehensive analysis of the two databases using the STRING database to construct a protein interaction network,and analyzed patient prognosis data based on the level of core gene expression.Results GSEA showed that the genes of pCR and npCR in GSE45670 were significantly different in cell cycle,DNA replication and other biological characteristics(nominal P<0.05 and FDR<0.25),and 70 radiosensitivity-related genes were identified.According to edgeR analysis,4855 differential genes were screened between esophageal squamous cell carcinoma and normal tissues in TCGA.Combining the two databases and the STRING database,a total of 46 genes were associated with esophageal squamous cell carcinoma and radiosensitivity,and could be used as candidate genes. Survival analysis showed that PRIM1 and PRKDC were highly expressed in both tumor tissues and pCR groups, and the prognosis was better( P <0.05). Conclusion Based on GEO and TCGA databases, 46 genes were associated with the occurrence and radiosensitivity of esophageal squamous cell carcinoma, and 26 genes could be the core genes. PRKDC and PRIM1 were highly expressed in the pCR group and correlated well with the prognosis of the carcinoma.
作者
师小博
孙宇晨
龚拓拓
张晓智
车少敏
SHI Xiaobo;SUN Yuchen;GONG Tuotuo;ZHANG Xiaozhi;CHE Shaomin(Department of Radiation Oncology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2020年第5期651-658,共8页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
陕西省重点研发计划重点资助项目(No.2018ZDXM-SF-043)。
关键词
食管鳞状细胞癌
放射敏感性
生物信息学分析
预后
esophageal squamous cell carcinoma
radiosensitivity
bioinformatics analysis
prognosis
作者简介
通信作者:张晓智,主任医师,教授,博士研究生导师.E-mail:zhang9149@sina.com;通信作者:车少敏,副主任医师,教授.E-mail:chersm@126.com。
