基于生物信息学方法对胰腺癌血浆差异miRNA和基因表达的分析研究

Analysis of differential miRNA and gene expression in plasma of pancreatic cancer based on bioinformatics method

目的采用生物信息学方法进一步筛选和验证胰腺癌血浆标志物,为明确其分子机制提供依据。方法通过关键词“胰腺癌、血浆、miRNA”进行检索,搜集文献,并下载原始数据,进行生物信息学分析,寻找具有特异性的血浆miRNA标志物,预测其靶基因,进行通路富集和互作分析,通过文献数据和数据库进行关键基因的验证,分析其差异表达谱及其与胰腺癌预后的关系。结果通过对GSE59856和GSE124158进行差异miRNA的筛选,最后筛选得出miR-122-5p。通过对miR-122-5p预测得到了517个靶基因,并对靶基因作GO/KEGG富集分析。进一步对靶基因做蛋白互作图,并通过相关文献的查询与筛查,筛选出UBA52、ADAM10、CBL、VAMP3这4个关键基因。根据TCGA表达谱及文献数据论证,与健康人相比,胰腺癌患者高表达UBA52、ADAM10、CBL、VAMP3。VAMP3、ADAM10基因低表达的胰腺癌患者总体生存率更高(P<0.05)。结论采用生物信息学方法对胰腺癌患者血浆差异miRNA进行分析,筛选出的miR-122-5p具有作为胰腺癌诊断标志物的潜力。miR-122-5p作用的关键靶基因VAMP3、ADAM10与胰腺癌的预后密切相关。

Objective The bioinformatics method were used to further screen and verify the plasma markers of pancreatic cancer,which provide a basis for clarifying its molecular mechanism.Methods The retrieval was performed by the Keyword"pancreatic cancer""serum""miRNA"for collecting the literatures and downloading the original data.The bioinformatics analysis was conducted to find specific serum miRNAs markers,and predict their target genes.The pathway enrichment and transactional analysis were performed.The key genes were verified by the literature data and databases.The differential expression profile and its relationship with the prognosis of pncreatic cancer were analyzed.Results The differential miRNA screening of GSE59856 and GSE124158 were performed,miR-122-5p was finally screened out.Then,517 target genes were obtained by predicting miR-122-5p and the target gene conducted the GO/KEGG enrichment analysis.The targeted genes further conducted the protein interaction mapping.By the related literature inquiring and screening,the four key genes were screened out,including UBA52,ADAM10,CBL and VAMP3.According to TCGA expression profile and literature data argument,compared with the healthy people,UBA52,ADAM10,CBL and VAMP3 were highly expressed in the patients with pancreatic cancer.The pancreatic cancer patients with low expression of VAMP3 and ADAM10 genes had higher overall survival rate.Conclusion Adopting the bioinformatics method to conduct the plasma differential miRNA analysis,the screened miR-122-5p has the potential as the biomarker for the diagnosis of pancreatic cancer.The key target genes VAMP3 and ADAM10 of miR-122-5p are closely related to the prognosis of pancreatic cancer.