Sheng Xia, Huang Tao, Qin Jianmin, Yang Lin, Sa Zhong-Qiu, Li Qi
1 Department of pathology, Affiliated to the Third Hospital, Second Military Medical University, Shanghai, P.R. China.
2 Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
Technol Cancer Res Treat. 2018 Jan 1;17:1533034618756785. doi: 10.1177/1533034618756785.
The pathogenesis of hepatocellular carcinoma is complex and not fully known yet. This study aims to screen and identify the differentially expressed proteins in peripheral blood and liver tissue samples from rat hepatocellular carcinoma and to further clarify the pathogenesis and discover the specific tumor markers and molecular targets of hepatocellular carcinoma. The hepatocellular carcinoma model of Wistar rats were induced by chemical carcinogen. The serum and liver tissue samples were obtained after induction for 2, 4, 8, 14, 18, and 21 weeks. The results showed that the clusterin (IPI00198667), heat shock protein a8 (IPI00208205), and N-myc downstream-regulated gene-2 (IPI00382069) being closely related to hepatocarcinogenesis were eventually identified from the 30 different proteins. As the time progressed, the serum levels of clusterin and heat shock protein a8 increased gradually during induced liver cancer in rats. However, the serum N-myc downstream-regulated gene 2 level in induced liver cancer in rats underwent biphasic changes, and the serum N-myc downstream-regulated gene 2 level decreased at the 8th week, increased at the 14th week, and then decreased significantly. Statistical difference occurred in protein expression of clusterin and heat shock protein a8 in liver tissues at the different time points. In the liver tissues, the N-myc downstream-regulated gene 2 level decreased gradually at the 8th week, increased gradually at the 14th week, and then decreased significantly after 14 weeks. The study demonstrated that heat shock protein a8, clusterin, and N-myc downstream-regulated gene 2 participated in the process of abnormal cell division, proliferation, and carcinogenesis of liver cells during hepatocarcinogenesis.
肝细胞癌的发病机制复杂，目前尚未完全明确。本研究旨在筛选并鉴定大鼠肝细胞癌外周血和肝组织样本中差异表达的蛋白质，以进一步阐明其发病机制，发现肝细胞癌的特异性肿瘤标志物和分子靶点。采用化学致癌物诱导建立Wistar大鼠肝细胞癌模型。诱导2、4、8、14、18和21周后获取血清和肝组织样本。结果显示，最终从30种不同蛋白质中鉴定出与肝癌发生密切相关的簇集素（IPI00198667）、热休克蛋白α8（IPI00208205）和N - myc下游调节基因2（IPI00382069）。随着时间推移，大鼠诱导性肝癌过程中簇集素和热休克蛋白α8的血清水平逐渐升高。然而，大鼠诱导性肝癌中血清N - myc下游调节基因2水平呈双相变化，在第8周降低，第14周升高，随后显著降低。不同时间点肝组织中簇集素和热休克蛋白α8的蛋白表达存在统计学差异。在肝组织中，N - myc下游调节基因2水平在第8周逐渐降低，第14周逐渐升高，14周后显著降低。该研究表明，热休克蛋白α8、簇集素和N - myc下游调节基因2参与了肝癌发生过程中肝细胞异常分裂、增殖和致癌的过程。
