Liang Hong-jie, Wei Wei, Kang Xiao-nan, Guo Kun, Cao Ji, Su Jian-jia, Yang Chun, Ou Chao, Li Yuan, Liu Yin-kun
Department of Laboratory Medicine, the First Hospital Affiliated to Guangxi Medical University, Nanning 530021, China.
Zhonghua Gan Zang Bing Za Zhi. 2009 Sep;17(9):669-74.
To screen the differentially expressed proteins especially at the precancerous stage of diethylnitrosamine (DEN) induced hepatocarcinogenesis by comparative proteome research.
Rats were divided into normal and DEN groups and sacrificed periodically. The liver samples were stained with gamma-glutamyl transpeptidase (GGT) and HE to distinguish the preneoplastic lesion (pre-HCC) from the normal and HCC tissues. The two-dimensional electrophoresis (2-DE) and mass spectrometry (MALDI-TOF-MS/MS) were then applied to analyze the differentially expressed protein between pre-HCC and normal tissues, pre-HCC and HCC, as well as HCC and normal tissues. A few of the candidate proteins such as laminin receptor 1 (67LR) and agmatinase were validated by Western blot and RT-PCR.
Totally, there were 82 proteins that differentially expressed two fold or more in one kind of tissues sample than the other, 47 of which occurred in the pre-HCC tissues. Eight proteins including 67LR were consistently up-regulated from normal tissue to pre-HCC and then to HCC tissues, while 22 proteins including agmatinase showed progressively down-regulated in these tissues samples.
The protein expression profiles are different during the process of hepatocarcinogenesis. Further study on the differentially expressed protein, especially these upregulated in the precancerous stage such as 67LR and agmatinase, might contribute to prevention and early diagnosis of human HCC.
通过比较蛋白质组学研究，筛选在二乙基亚硝胺（DEN）诱导的肝癌发生癌前阶段差异表达的蛋白质。
将大鼠分为正常组和DEN组，并定期处死。肝组织样本用γ-谷氨酰转肽酶（GGT）和苏木精-伊红（HE）染色，以区分癌前病变（癌前肝癌）与正常和肝癌组织。然后应用二维电泳（2-DE）和质谱（MALDI-TOF-MS/MS）分析癌前肝癌与正常组织、癌前肝癌与肝癌以及肝癌与正常组织之间差异表达的蛋白质。通过蛋白质免疫印迹法（Western blot）和逆转录-聚合酶链反应（RT-PCR）对层粘连蛋白受体1（67LR）和精氨酸酶等几种候选蛋白进行验证。
共有82种蛋白质在一种组织样本中比另一种组织样本差异表达两倍或更多，其中47种出现在癌前肝癌组织中。包括67LR在内的8种蛋白质从正常组织到癌前肝癌再到肝癌组织持续上调，而包括精氨酸酶在内的22种蛋白质在这些组织样本中逐渐下调。
肝癌发生过程中蛋白质表达谱不同。对差异表达蛋白质，尤其是在癌前阶段上调的蛋白质如67LR和精氨酸酶进行进一步研究，可能有助于人类肝癌的预防和早期诊断。
