长链非编码RNA在宫颈癌中的表达及预后价值

Expression of lncRNA in cervical cancer and its prognostic values

目的研究长链非编码RNA(lncRNA)在宫颈癌中的表达水平,鉴定在宫颈癌组织中异常表达的lncRNA,初步分析其功能,并评估其预后价值。方法宫颈癌组织和癌旁组织的转录组数据下载自癌症基因组图谱(TCGA),结合Genecode数据库中lncRNA注释信息,获取lncRNA的表达数据。通过limma软件包鉴定在宫颈癌组织和癌旁组织中差异表达的lncRNA;同时对存在差异表达的lncRNA进行生存分析和功能预测。结果在宫颈癌组织和癌旁组织中差异表达的lncRNA有554个,其中在宫颈癌组织中表达下调245个,上调309个(校正后P<0.05,倍数变化绝对值>2)。生存分析鉴定出11个与宫颈癌患者总体生存率相关的差异表达lncRNA(P<0.01)。京都基因与基因组百科全书(KEGG)代谢途径富集分析显示这些lncRNA参与到环磷酸鸟苷酸-环磷酸鸟苷酸依赖的蛋白激酶(cGMP-PKG)信号通路、钙信号通路和细胞间隙连接等肿瘤发生、发展相关代谢途径。结论通过对宫颈癌lncRNA数据的分析,鉴定11个具有预后意义的lncRNA,这些lncRNA有可能为宫颈癌治疗提供新的靶点和预后监测标志物。

Objective To detect the expression of long non-coding RNAs(lncRNAs)in cervical cancer,and to analyze their function and prognostic values.Methods RNA-Seq data of cervical cancer and normal adjacent tissues were downloaded from the website of The Cancer Genome Altas(TCGA).Combined with the annotation file downloaded from the Genecode database,the expression of mRNA and lncRNA was obtained.Then differential expression analysis was conducted with limma package in R software.The prognostic value of lncRNA was assessed by survival analysis.The mRNAs co-expressed with the differentially expressed lncRNAs were identified and subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results 554 lncRNAs were identified as differentially expressed lncRNAs between cervical cancer and normal adjacent tissues.Among these lncRNAs,245 lncRNAs were down-regulated and 309 lncRNAs up-regulated in cervical cancer(adjusted P<0.05 and absolute fold change>2).Survival analysis revealed 11 lncRNAs that were prognostic of patient overall survival(P<0.05).KEGG enrichment analysis showed that these prognostic related lncRNAs were involved in the processes that related to the development and progression of tumors,such as cGMP-PKG signaling pathway,Calcium signaling pathway,ABC transporters and Gap junction.Conclusions We identified 11 prognostic related lncRNAs.The discoveries made in this study may serve as therapeutic targets or biomarkers to facilitate targeted therapy and prognostication of cervical cancer.