摘要
目的:旨在基于TCGA数据库构建宫颈鳞状细胞癌(CSCC)放疗抵抗竞争性内源性RNA(ceRNA)网络,鉴定潜在的预测放疗疗效生物标志物及探讨放疗抵抗的机制。方法:依据纳入研究标准在TCGA数据库的宫颈癌数据集中筛选出23个CSCC放疗抵抗与67个放疗敏感样本的RNA表达谱数据,运行R"edger"包鉴定差异表达lncRNAs、miRNAs和mRNAs,基于miRcode、TargetScan和miRTarBase数据库构建ceRNA网络并通过Cytoscape软件可视化。进一步结合KEGG、GO及生存分析等生物信息学方法筛选出关键分子。结果:设定阈值为|log2差异倍数(FC)|>1.5且FDR<0.05,共鉴定出237个DElncRNAs,16个DEmiRNAs和565个DEmRNAs,其中17个DElncRNAs、3个DEmiRNAs和15个DEmRNAs参与构建ceRNA网络。DEmRNAs富集到3个GO术语和8个KEGG途径(P<0.05)。5个DElncRNAs在不同临床病理特征中有显著差异(|log2FC|>2且FDR<0.05)。结论:成功构建CSCC放疗抵抗特异性lncRNA相关的ce RNA网络,鉴定了预测CSCC放疗疗效分子标志物,为理解CSCC产生放疗抵抗的机制提供理论依据。
Objective:The aim of this study was to construct a competitive endogenous RNA(ceRNA)network,identify potential biomarkers and explore the mechanism of radiotherapy resistance among cervical squamous cell carcinoma(CSCC)patients based on TCGA database.Methods:The RNA expression profiles of 23 CSCC radiotherapy resistant and 67 radiotherapy sensitive samples were screened by inclusion criteria.The differentially expressed lncRNAs,microRNAs and mRNAs were identified by using R"edger"package.The ceRNA network was constructed based on microcode,TargetScan and miRTarBase databases and visualized by Cytoscape.The key molecules were screened by bioinformatics methods including KEGG,GO and survival analysis.Results:A total of 237 DElncRNAs,16 DEmiRNAs and 565 DEmRNAs were identified with thresholds of|log2(FC)|>1.5 and FDR<0.05.The new ceRNA network in radiotherapy-resistant CSCC was composed of 17 DElncRNAs,3 DEmiRNAs and 15 DEmRNAs.3 GO terms and 8 KEGG pathways were significantly enriched by the DEmRNAs.Further,5 DElncRNAs were found to be associated with clinical features.Conclusion:We successfully constructed a ceRNA network associated with specific lncRNA resistance to CSCC radiotherapy,identified molecular markers predicting the efficacy of CSCC radiotherapy,and provided a possible theoretical basis for understanding the mechanism of radiation resistance of CSCC.
作者
吴南昌
陈昌贤
陶珊
李世婷
任遥瑶
宋红林
Wu Nanchang;Chen Changxian;Tao Shan;Li Shiting;Ren Yaoyao;Song Honglin(Guangxi Medi cal University,Nanning 530021,China;Department of Gynecologic Oncology,Guangxi Medical University Cancer Hospital,Nanning 530021,China)
出处
《广西医科大学学报》
CAS
2020年第1期23-28,共6页
Journal of Guangxi Medical University
基金
广西医疗卫生适宜技术研究与开发资助项目(No.S201510)
广西医科大学区域性高发肿瘤早期防治研究教育部重点实验室课题资助项目(No.GKE2018-10)。
关键词
宫颈鳞癌
放疗抵抗
竞争性内源性RNA
长链非编码RNA
癌症基因组图谱
cervical squamous cell carcinoma
radiotherapy resistance
competitive endogenous RNA
long noncoding RNA
cancer genome atlas
