Xie Feng, Zhu Fang, Lu Zaiming, Liu Zhengrong, Wang Hongyan
Department of Nuclear Medicine, The People's Hospital of Liaoning, Shenyang, Liaoning 110016, P.R. China.
Cardiovascular Center, The People's Hospital of Liaoning, Shenyang, Liaoning 110016, P.R. China.
Oncol Lett. 2016 Jul;12(1):495-503. doi: 10.3892/ol.2016.4615. Epub 2016 May 24.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China and the third leading cause of cancer-associated morality. The aim of the present study was to investigate and analyze differentially-expressed genes (DEGs) between cirrhosis and HCC, in order to screen the key genes involved in the transformation from cirrhosis to HCC and provide novel targets for the diagnosis and treatment of HCC in patients with cirrhosis. The gene expression profile, GSE17548, was obtained from Gene Expression Omnibus database and the DEGs were identified by LIMMA package in R language. Kyoto Encyclopedia of Genes and Genomes and gene ontology biology process analysis were performed for the DEGs. Differential co-expression network (DEN) analysis was conducted and the network was visualized using Cytoscape. Small molecule drugs were also screened from the Comparative Toxicogenomics Database for higher degree DEGs. A total of 95 DEGs were obtained, including 46 upregulated and 49 downregulated genes. The upregulated DEGs were primarily involved in biological processes and pathways associated with the cell cycle, while the downregulated DEGs were primarily involved in immune-associated biological processes. A total of 22 key DEGs were identified by DEN analysis, which distinguished HCC from cirrhosis samples. Furthermore, estradiol, benzo(a)pyrene, acetaminophen, copper sulfate and bisphenol A were identified as the five most associated chemicals to these 22 DEGs. In conclusion, the hub genes and chemicals identified by the present study may provide a theoretical basis for additional research on diagnosis and treatment of HCC transformed from cirrhosis.
肝细胞癌(HCC)是中国最常见的恶性肿瘤之一,也是癌症相关死亡的第三大主要原因。本研究的目的是调查和分析肝硬化与HCC之间的差异表达基因(DEG),以筛选参与从肝硬化转变为HCC的关键基因,并为肝硬化患者HCC的诊断和治疗提供新的靶点。从基因表达综合数据库中获取基因表达谱GSE17548,并使用R语言中的LIMMA软件包鉴定DEG。对DEG进行京都基因与基因组百科全书和基因本体生物学过程分析。进行差异共表达网络(DEN)分析,并使用Cytoscape可视化该网络。还从比较毒理基因组学数据库中筛选了针对高程度DEG的小分子药物。共获得95个DEG,包括46个上调基因和49个下调基因。上调的DEG主要参与与细胞周期相关的生物学过程和途径,而下调的DEG主要参与免疫相关的生物学过程。通过DEN分析鉴定出总共22个关键DEG,其可区分HCC与肝硬化样本。此外,雌二醇、苯并(a)芘、对乙酰氨基酚、硫酸铜和双酚A被确定为与这22个DEG最相关的五种化学物质。总之,本研究鉴定出的枢纽基因和化学物质可能为进一步研究肝硬化转化而来的HCC的诊断和治疗提供理论依据。