Liu Yuefang, Zhu Xiaojing, Zhu Jin, Liao Shibing, Tang Qi, Liu Kaikun, Guan Xiaohong, Zhang Jianping, Feng Zhenqing
Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 210029, PR China.
Oncol Rep. 2007 Oct;18(4):943-51.
The genetic background of hepatocellular carcinoma (HCC) has yet to be completely understood. Here, we describe the application of suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis for the isolation and identification of differential expression of genes in HCC. Twenty-six known genes were validated as up-regulated and 19 known genes as down-regulated in HCC. The known genes identified were found to have diverse functions. In addition to the overexpression of AFP, these genes (increased in the presence of HCC) are involved in many processes, such as transcription and protein biosynthesis (HNRPDL, PABPC1, POLR2K, SRP9, SNRPA, and six ribosomal protein genes including RPL8, RPL14, RPL41, RPS5, RPS17, RPS24), the metabolism of lipids and proteins (FADS1, ApoA-II, ApoM, FTL), cell proliferation (Syndecan-2, and Annexin A2), and signal transduction (LRRC28 and FMR1). Additionally, a glutathione-binding protein involved in the detoxification of methylglyoxal known as GLO1 and an enzyme which increases the formation of prostaglandin E(2) known as PLA2G10 were up-regulated in HCC. Among the underexpressed genes discovered in HCC, most were responsible for liver-synthesized proteins (fibrinogen, complement species, amyloid, albumin, haptoglobin, hemopexin and orosomucoid). The enzyme implicated in the biotransformation of CYP family members (LOC644587) was decreased. The genes coding enzymes ADH1C, ALDH6A1, ALDOB, Arginase and CES1 were also found. Additionally, we isolated a zinc transporter (Zip14) and a function-unknown gene named ZBTB11 (Zinc finger and BTB domain containing 11) which were underexpressed, and seven expression sequence tags deregulated in HCC without significant homology reported in the public database. Essentially, by using SSH combined with a cDNA microarray we have identified a number of genes associated with HCC, most of which have not been previously reported. Further characterization of these differentially expressed genes will provide information useful in understanding the genes responsible for the development of HCC.
肝细胞癌（HCC）的遗传背景尚未完全明确。在此，我们描述了抑制性消减杂交（SSH）与cDNA微阵列分析相结合在分离和鉴定HCC中差异表达基因方面的应用。26个已知基因被证实为在HCC中上调，19个已知基因被证实为在HCC中下调。所鉴定的已知基因具有多种功能。除甲胎蛋白（AFP）过表达外，这些基因（在HCC存在时增加）参与许多过程，如转录和蛋白质生物合成（HNRPDL、PABPC1、POLR2K、SRP9、SNRPA以及包括RPL8、RPL14、RPL41、RPS5、RPS17、RPS24在内的六个核糖体蛋白基因）、脂质和蛋白质代谢（FADS1、ApoA-II、ApoM、FTL）、细胞增殖（Syndecan-2和膜联蛋白A2）以及信号转导（LRRC28和FMR1）。此外，一种参与甲基乙二醛解毒的谷胱甘肽结合蛋白GLO1和一种增加前列腺素E(2)形成的酶PLA2G10在HCC中上调。在HCC中发现的低表达基因中，大多数负责肝脏合成的蛋白质（纤维蛋白原、补体成分、淀粉样蛋白、白蛋白、触珠蛋白、血红素结合蛋白和orosomucoid）。参与细胞色素P450家族成员生物转化的酶（LOC644587）减少。还发现了编码酶ADH1C、ALDH6A1、ALDOB、精氨酸酶和CES1的基因。此外，我们分离出一个锌转运体（Zip14）和一个名为ZBTB11（含锌指和BTB结构域11）的功能未知基因，它们在HCC中低表达，以及七个在HCC中失调且在公共数据库中未报告有显著同源性的表达序列标签。本质上，通过使用SSH结合cDNA微阵列，我们鉴定了许多与HCC相关的基因，其中大多数以前未曾报道过。对这些差异表达基因的进一步表征将为理解导致HCC发生的基因提供有用信息。
