Integrated Analysis of Copy Number Variations and Gene Expression Profiling in Hepatocellular carcinoma.
Integrated Analysis of Copy Number Variations and Gene Expression Profiling in Hepatocellular carcinoma.
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肝细胞癌拷贝数变异和基因表达谱的综合分析
DOI：
10.1038/s41598-017-11029-y
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发表时间：
2017-09-05
影响因子：
4.6
通讯作者：
Ren N
中科院分区：
文献类型：
--
作者：
Zhou C;Zhang W;Chen W;Yin Y;Atyah M;Liu S;Guo L;Shi Y;Ye Q;Dong Q;Ren N
肝细胞癌（HCC）是全球三大癌症杀手之一。本研究将拷贝数变异（CNVs）分析与基因表达谱分析相结合，旨在寻找HBV相关HCC中CNV驱动的差异表达基因（DEG）。CNVs区域中的重要基因与表达谱中获得的基因重叠。获得了93个在复制区表现出表达增加的CNV驱动基因和45个在缺失区表现出表达降低的CNV驱动基因，其中复制和缺失主要记录在1号和4号染色体上。分别使用大卫和KOBAS进行功能和途径富集分析。它们主要富集在代谢过程和细胞周期中。利用Cytoscape软件构建蛋白质相互作用（PPI）网络，筛选出4个中心基因。随后，生存分析表明，只有高NPM1表达与HCC患者的生存率和复发率显著相关。此外，这种相关性在早期HCC患者中仍然显著。此外，我们发现NPM1在HCC细胞和HCC与邻近非肿瘤组织中过表达。总之，这些结果表明，基因组和表达谱的综合分析可能提供了一个强大的潜力，以确定CNV驱动的基因在HBV相关的肝癌发病机制。
Hepatocellular carcinoma (HCC) is one of the top three cancer killers worldwide. To identify CNV-driven differentially expressed genes (DEGs) in HBV related HCC, this study integrated analysis of copy number variations (CNVs) and gene expression profiling. Significant genes in regions of CNVs were overlapped with those obtained from the expression profiling. 93 CNV-driven genes exhibiting increased expression in the duplicated regions and 45 showing decreased expression in the deleted regions were obtained, which duplications and deletions were mainly documented at chromosome 1 and 4. Functional and pathway enrichment analyses were performed using DAVID and KOBAS, respectively. They were mainly enriched in metabolic process and cell cycle. Protein-protein interaction (PPI) network was constructed by Cytoscape, then four hub genes were identified. Following, survival analyses indicated that only high NPM1 expression was significantly and independently associated with worse survival and increased recurrence in HCC patients. Moreover, this correlation remained significant in patients with early stage of HCC. In addition, we showed that NPM1 was overexpressed in HCC cells and in HCC versus adjacent non-tumor tissues. In conclusion, these results showed that integrated analysis of genomic and expression profiling might provide a powerful potential for identifying CNV-driven genes in HBV related HCC pathogenesis.
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影响因子：
158.5
作者：
Falini, B;Mecucci, C;Martelli, MF
通讯作者：
Martelli, MF
DOI：
10.1093/bioinformatics/bts251
发表时间：
2012-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jiao X;Sherman BT;Huang da W;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW
影响因子：
13.5
作者：
Chen, Chian-Feng;Hsu, En-Chi;Jou, Yuh-Shan
通讯作者：
Jou, Yuh-Shan
影响因子：
10.6
作者：
Kirov, George;Rees, Elliott;Walters, James T. R.;Escott-Price, Valentina;Georgieva, Lyudmila;Richards, Alexander L.;Chambert, Kimberly D.;Davies, Gerwyn;Legge, Sophie E.;Moran, Jennifer L.;McCarroll, Steven A.;O'Donovan, Michael C.;Owen, Michael J.
通讯作者：
Owen, Michael J.