宫颈癌新miRNA分子标记物发掘与功能分析
Discovery of new miRNA biomarkers for cervical and endocervical cancer (CESC) from RNA-seq
摘要目的 由于宫颈癌的临床确诊与预后不佳,急需寻找到用于筛查宫颈癌发病过程的生物标志物.方法 本文通过对TCGA数据库中来源于宫颈癌样本的高通量转录组测序(含mRNA及miRNA)进行生物信息学数据挖掘,筛选在癌症和癌旁组织中差异表达的miRNA及mRNA,并与宫颈癌患者的临床数据做关联分析.结果 从18个差异表达的miRNA中筛选出4个miRNA(hsa-mir-101-2、hsa-mir-128-1、hsa-mir-145和hsa-mir-642a)与宫颈癌的生存显著相关,可作为宫颈癌的生物标志物;同时系统分析了这4个miRNA的下游1037个靶基因及其所参与的信号通路(如MAPK信号通路、FOXO信号通路和miRNA in Cancer信号通路).结论 宫颈癌患者中这四个差异表达的miRNA(mir-hsa-mir-101-2、hsa-mir-128-1、hsa-mir-145和hsa-mir-642a)可作为宫颈癌的生物标志物,对转录组数据的深入挖掘为宫颈癌的深入研究提供新的思路.
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abstractsObjective To identify the biomarkers for cervical and endocervical cancer (CESC),an urgent healthcare issue because of the poor diagnosis and prognosis of this cancer.Methods In this study,taking advantage of the high-throughput RNA-seq data from The Cancer G enome Atlas (TCGA),we profiled differentially expressed miRNA and mRNA genes between tumor and normal tissues.Meanwhile we performed correlation analysis to establish the link between differentially expressed miRNAs and clinic data.Results We screened four miRNAs (hsa-mir-101-2,hsa-mir-128-1,hsa-mir-145 and hsa-mir-642a) from 18 dysregulated miRNAs,which were closely related to the survival of CESC patients and could be used as biomarkers of CESC.In addition,we also systematically explored the target genes by the four miRNAs and their possible signaling pathways.Conclusion The four miRNAs (hsa-mir-101-2,hsa-mir-128-1,hsa-mir-145and hsa-mir-642a) could be used as biomarkers during the pathogenesis of CESC.Our data-mining work on miRNAs,dysregulated target genes and signaling pathways provides new insights into the further study at CESC.
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