摘要
目的探讨通过PIL法和通路富集分析法,预测与宫颈癌相关的潜在mRNA及调控miRNA,证实相关分子调控通路的可靠性和有效性。方法PIL法是以Borda选举算法为基础,将皮尔逊相关系数(PCC)、因果推理法(IDA)和回归法(Lasso)三者结合,形成的"PIL"综合分析方法。本研究首先分别采用PCC、IDA、Lasso三种方法筛选数据库中宫颈癌相关miRNA及负向调控靶基因。之后,将PIL法预测结果与miRNA数据库中已经试验证实的靶基因及其调控micro RNA(miRNA)的调控信息进行对比验证。最后,通过PIL法筛选出TCGA数据库内与宫颈癌发病最相关即相互作用最显著的1000个mRNA及调控miRNA,采用KEGG数据库进行信号转导通路富集分析,发现与宫颈癌最具有相关性的靶通路。结果PIL法共获得10个预测频率>5次的靶基因,包括分泌型卷曲相关蛋白4(SFRP44),母系表达基因3(MEG3)和NIPA样结构域(NIPA 4)。KEGG数据库从所有信号通路中共鉴定出17个与宫颈癌最具显著相关性的细胞因子-受体作用目标通路(P=8.91×10-7)。结论通过PIL综合分析法进行miRNA数据库资料采集、靶基因筛选、信号通路分析可行、可靠。
Objective To discriminate potential target genes and pathways in patients with CC by utilizing an ensemble method(PIL)and pathway enrichment analysis.Methods The ensemble method integrated a correlation method[Pearson’s correlation coefficient(PCC)],a causal inference method(IDA)and a regression method[least absolute shrinkage and selection operator(Lasso)]using the Borda count election algorithm,forming the PCC,IDA and Lasso(PIL)method.Consequently,the PIL method was validated to be a feasible approach to predict microRNA(miRNA)targets by comparing predicted miRNA targets against those from a experiment-confrmed database.Finally,Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was carried out for target genes in the 1000 most frequently predicted miRNA-mRNA interactions to determine target pathways.Results A total of 10 target genes were aquired which were predicted>5 times,including secreted frizzled-related protein 4,maternally expressed 3 and NIPA like domain containing 4.Moreover,a total of 17 target pathways were recognized,of which cytokine-cytokine receptor interaction(P=8.91×10-7)was the most importantly associated with CC of all target pathways.Conclusion By PIL comprehensive analysis method of micrornas database acquisition,target gene screening,signaling pathway analysis is feasible and reliable.
作者
尉文功
陈锐
WEI Wen-gong;CHEN Rui(Department of Gynecology,Qingpu Branch of Zhongshan Hospital in Fudan University,Shanghai 201700,China;Department of Gynecology,East Hospital Affiliated to Tongji University,Shanghai 200120,China)
出处
《哈尔滨医科大学学报》
CAS
2019年第6期587-592,共6页
Journal of Harbin Medical University
