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宫颈癌中的微小RNA表达:新型诊断和预后生物标志物

MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers.

作者信息

Gao Chundi, Zhou Chao, Zhuang Jing, Liu Lijuan, Liu Cun, Li Huayao, Liu Gongxi, Wei Junyu, Sun Changgang

机构信息

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P. R. China.

Departmen of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, P. R. China.

出版信息

J Cell Biochem. 2018 Aug;119(8):7080-7090. doi: 10.1002/jcb.27029. Epub 2018 May 8.

Abstract

Growing evidence has shown that a large number of miRNAs are abnormally expressed in cervical cancer (CC) tissues and play irreplaceable roles in tumorigenesis, progression, and metastasis. This study aimed to identify new biomarkers and pivotal genes associated with CC prognosis through comprehensive bioinformatics analysis. At first, the data of gene expression microarray (GSE30656) was downloaded from GEO database and differential miRNAs were obtained. Additionally, 4 miRNAs associated with the survival time of patients with CC were screened through TCGA differential data analysis, Kaplan-Meier, and Landmark analysis. Among them, the low expression of miR-188 and high expression of miR-223 correlated with the short survival of CC patients, while the down-regulation of miR-99a and miR-125b was closely related to the 5-year survival rate of patients. Then, based on the correspondence between the differentially expressed genes (DEGs) in CC from the TCGA data and the 4 miRNAs target genes, 58 target genes were screened to perform the analysis of function enrichment and the visualization of protein-protein interaction (PPI) networks. The seven pivotal genes of the PPI network as the target genes of four miRNAs related to prognosis, they were directly or indirectly involved in the development of CC. In this study, based on high-throughput data mining, differentially expressed miRNAs and related target genes were analyzed to provide an effective bioinformatics basis for further understanding of the pathogenesis and prognosis of CC. And the results may be a promising biomarker for the early screening of high-risk populations and early diagnosis of cervical cancer.

摘要

越来越多的证据表明,大量的微小RNA(miRNA)在宫颈癌(CC)组织中异常表达,并在肿瘤发生、发展和转移中发挥着不可替代的作用。本研究旨在通过综合生物信息学分析,鉴定与CC预后相关的新生物标志物和关键基因。首先,从基因表达综合数据库(GEO)下载基因表达微阵列(GSE30656)数据,并获得差异miRNA。此外,通过TCGA差异数据分析、Kaplan-Meier分析和地标分析,筛选出4个与CC患者生存时间相关的miRNA。其中,miR-188低表达和miR-223高表达与CC患者的短生存期相关,而miR-99a和miR-125b的下调与患者的5年生存率密切相关。然后,基于TCGA数据中CC差异表达基因(DEG)与4个miRNA靶基因的对应关系,筛选出58个靶基因进行功能富集分析和蛋白质-蛋白质相互作用(PPI)网络可视化。PPI网络中的7个关键基因作为与预后相关的4个miRNA的靶基因,它们直接或间接参与了CC的发生发展。本研究基于高通量数据挖掘,分析了差异表达的miRNA和相关靶基因,为进一步了解CC的发病机制和预后提供了有效的生物信息学依据。研究结果可能为宫颈癌高危人群的早期筛查和早期诊断提供有前景的生物标志物。

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