基于GEO数据库的卵巢癌ceRNA调控网络构建及相关lncRNAs的筛选

Construction of ovarian cancer lncRNA-related ceRNA network and identification of novel lncRNAs

目的基于卵巢癌相关的非编码RNA高通量测序数据,构建竞争性内源RNA(ceRNA)调控网络并进行功能富集分析,研究筛选参与的卵巢癌发生和发展的lncRNAs。方法采用GEO数据库的RNA-seq测序数据和miRNA-seq测序数据,筛选差异表达的长非编码RNA(lncRNAs),miRNAs和mRNAs,并根据ceRNA理论构建lncRNA-miRNA-mRNA调控网络。采用KOBAS工具对基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。采用R语言的pROC函数进行受试者工作特征ROC(曲线)分析。结果lncRNA FTX与PDS5B表现最高的正相关关系(R=0.91,P<0.001),GEO数据库分别获得22个差异lncRNAs,149个差异miRNAs和1409个差异mRNAs分子,并成功构建卵巢癌相关的ceRNA调控网络。GO和KEGG分析表明失调的mRNAs主要与TGF-β1调控,细胞增殖及补体信号通路等有关。结论本研究通过综合生物信息分析策略,构建卵巢癌特异性的lncRNA相关ceRNA调控网络,并鉴定lncRNA FTX可作为潜在的诊断分子靶标,为卵巢癌早期诊断提供参考。

Objective The present study aimed to construct a competitive endogenous RNA(ceRNA)regulatory network and perform functional enrichment analysis based on ovarian cancer(OC)-related non-coding RNA high-throughput sequencing data to screen lncRNAs involved in the progression and development in ovarian cancer.Methods The differentially expressed lncRNAs,miRNAs and mRNAs were screened based on the RNA-seq and miRNA-seq sequencing data from GEO database.Then the lncRNA-miRNA-mRNA regulatory network was constructed according to the ceRNA theory.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed using KOBAS tools.The receiver operating characteristic curve(ROC)analysis was performed using the pROC package in R language.Results A total of 22 differentially expressed lncRNAs,149 differentially expressed miRNAs and 1409 differentially expressed mRNAs were identified to construct OC-related ceRNA network.The results of GO and KEGG showed that these dysregulated genes were enriched in TGF-β1 regulation,cell proliferation and complement and coagulation cascades.The results of correlation showed the most significantly positive correlation between lncRNA FTX and PDS5B(R=0.91,P<0.001).Conclusion This study constructed lncRNA-mediated ceRNA network and selected out lncRNA FTX as potential diagnostic biomarker according to integrated bioinformatics analysis for the clinical diagnosis in early stage OC.