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通过生物信息学分析鉴定肝癌中拷贝数变异驱动的基因。

Identification of copy number variation-driven genes for liver cancer via bioinformatics analysis.

作者信息

Lu Xiaojie, Ye Kun, Zou Kailin, Chen Jinlian

机构信息

Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.

出版信息

Oncol Rep. 2014 Nov;32(5):1845-52. doi: 10.3892/or.2014.3425. Epub 2014 Aug 20.

DOI:10.3892/or.2014.3425
PMID:25174835
Abstract

To screen out copy number variation (CNV)-driven differentially expressed genes (DEGs) in liver cancer and advance our understanding of the pathogenesis, an integrated analysis of liver cancer-related CNV data from The Cancer Genome Atlas (TCGA) and gene expression data from EBI Array Express database were performed. The DEGs were identified by package limma based on the cut-off of |log2 (fold-change)|>0.585 and adjusted p-value<0.05. Using hg19 annotation information provided by UCSC, liver cancer-related CNVs were then screened out. TF-target gene interactions were also predicted with information from UCSC using DAVID online tools. As a result, 25 CNV-driven genes were obtained, including tripartite motif containing 28 (TRIM28) and RanBP-type and C3HC4-type zinc finger containing 1 (RBCK1). In the transcriptional regulatory network, 8 known cancer-related transcription factors (TFs) interacted with 21 CNV-driven genes, suggesting that the other 8 TFs may be involved in liver cancer. These genes may be potential biomarkers for early detection and prevention of liver cancer. These findings may improve our knowledge of the pathogenesis of liver cancer. Nevertheless, further experiments are still needed to confirm our findings.

摘要

为筛选出肝癌中拷贝数变异(CNV)驱动的差异表达基因(DEG),并加深我们对其发病机制的理解,我们对来自癌症基因组图谱(TCGA)的肝癌相关CNV数据和来自欧洲生物信息研究所阵列表达数据库的基因表达数据进行了综合分析。使用limma软件包,基于|log2(倍数变化)|>0.585和校正p值<0.05的阈值来鉴定DEG。利用加州大学圣克鲁兹分校(UCSC)提供的hg19注释信息,筛选出肝癌相关的CNV。还使用DAVID在线工具根据UCSC的信息预测转录因子-靶基因相互作用。结果,获得了25个CNV驱动的基因,包括含三重基序蛋白28(TRIM28)和含RanBP型和C3HC4型锌指蛋白1(RBCK1)。在转录调控网络中,8个已知的癌症相关转录因子(TF)与21个CNV驱动的基因相互作用,这表明其他8个TF可能参与肝癌的发生。这些基因可能是肝癌早期检测和预防的潜在生物标志物。这些发现可能会增进我们对肝癌发病机制的认识。然而,仍需要进一步的实验来证实我们的发现。

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