Identification of a microRNA signature associated with survivability in cervical squamous cell carcinoma.

Identification of a microRNA signature associated with survivability in cervical squamous cell carcinoma.
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DOI:
10.1371/journal.pone.0193625
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Liu P
Liu P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ma C;Zhang W;Wu Q;Liu Y;Wang C;Lao G;Yang L;Liu P

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本研究的目的是寻找能够预测宫颈鳞状细胞癌(CSCC)患者生存时间的潜在miRNA表达特征。在癌症基因组图谱(TCGA)数据门户中,在131名(训练队列)和130名(验证队列)患有CSCC的患者中测量了332种miRNA的表达。通过对训练数据集的考克斯比例风险回归模型鉴定miRNA表达特征,随后在独立的验证集中验证。Kaplan-Meier曲线和5年受试者工作特征分析用于评估miRNA签名的总生存率。进行miRNA特征基因靶标分析,然后构建调控网络。利用Gene Ontology和京都基因百科全书和基因组通路分析技术对miRNA标签的靶基因进行功能分析。在CSCC中鉴定了与存活性相关的hsa-mir-642 a和hsa-mir-378 c的2-miRNA表达特征。两者对CSCC的诊断及预后判断均有重要价值。在构建的miRNA标签-基因靶调控网络中,共获得345个miRNA标签-靶对,其中316个基因为has-mir-378 c和has-mir-642 a的靶基因。对靶基因的功能分析表明,MAPK信号通路、VEGF信号通路和内吞作用是最丰富的信号通路,涵盖了大部分基因。2-miRNA标签增加了CSCC的预后价值。对2-miRNAs的深入研究将为发现和开发新的分子预测方法以改善CSCC患者的预后提供重要的生物学见解。
The aim of this study is to find the potential miRNA expression signature capable of predicting survival time for cervical squamous cell carcinoma (CSCC) patients. The expression of 332 miRNAs was measured in 131 (Training cohort) and 130 (Validation cohort) patients with CSCC in the Cancer Genome Atlas (TCGA) data portal. The miRNA expression signature was identified by Cox Proportion Hazard regression model to the Training data set, and subsequently validated in an independent Validation set. Kaplan-Meier curves and the receiver operating characteristic analyses of 5 years were used to access the overall survival of miRNA signature. MiRNA signature-gene target analysis was performed, followed by the construction of the regulatory network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to explore the function of target genes of miRNA signature. A 2-miRNA expression signature of hsa-mir-642a and hsa-mir-378c associated with survivability was identified in CSCC. Both of them had a significant diagnostic and prognostic value of patients with CSCC. A total of 345 miRNA signature-target pairs were obtained in the miRNA signature-gene target regulatory network, in which 316 genes were targets of has-mir-378c and has-mir-642a. Functional analysis of target genes showed that MAPK signaling pathway, VEGF signaling pathway and endocytosis were the significantly enriched signal pathways that covered most genes. The 2-miRNA signature adds to the prognostic value of CSCC. In-depth interrogation of the 2-miRNAs will provide important biological insights that finding and developing novel molecularly prediction to improve prognosis for CSCC patients.
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