摘要
目的探讨细胞分裂周期相关蛋白5(CDCA5)、细胞外调节蛋白激酶(ERK)在肝细胞肝癌中的表达及临床意义。方法取260例原发性肝细胞肝癌患者的肝细胞肝癌组织,取52例肝脏良性病变患者的正常肝组织作为对照。蛋白质印迹法(Western blot)检测CDCA5、ERK、细胞周期蛋白依赖性激酶1(CDK1)、细胞周期蛋白B1(cyclin B1)的相对表达量;实时荧光定量逆转录聚合酶链反应(RT-PCR)测定CDCA5、ERK mRNA的相对表达量,并分析其与患者临床特征的关系。采用Pearson相关性分析CDCA5和ERK与肝细胞肝癌患者病理特征间的相关性。结果肝细胞肝癌组织中CDCA5、ERK mRNA的相对表达量均高于正常肝组织,差异均有统计学意义(P﹤0.05)。肝细胞肝癌组织中CDCA5、ERK、CDK1和cyclin B1蛋白的相对表达量均高于正常肝组织,差异均有统计学意义(P﹤0.05)。不同肿瘤直径、Edmondson分级、巴塞罗那临床肝癌(BCLC)分期、合并门静脉癌栓情况和甲胎蛋白(AFP)水平肝细胞肝癌患者肝细胞肝癌组织中CDCA5、ERK mRNA的相对表达量比较,差异均有统计学意义(P﹤0.05)。CDCA5、ERK的表达与Edmondson分级为Ⅲ~Ⅳ级、BCLC分期为B~C期、有门静脉癌栓和AFP水平升高呈正相关(P﹤0.05)。结论CDCA5可能依赖ERK的磷酸化来促进CDK1、cyclin B1的表达,促进肿瘤细胞的恶性增殖,临床有望将其作为治疗肝细胞肝癌的新靶点。
Objective To explore the expression and clinical significance of cell division cycle associated 5(CDCA5) and extracellular regulated protein kinase(ERK) in hepatocellular carcinoma. Method Hepatocellular carcinoma tissues from 260 patients with primary hepatocellular carcinoma were collected, and normal hepatic tissues from 52 patients with benign liver disease were taken as controls. Western blot detection of CDCA5, ERK, cyclin dependent kinase 1(CDK1), cyclin B1 protein relative expression. The relative expression of CDCA5 mRNA and ERK mRNA were measured by real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR), and analyzes the relationship between them and the clinical characteristics of patients. The correlation between CDCA5 and ERK and the pathological characteristics of hepatocellular carcinoma patients was tested by Pearson correlation. Result The relative expression of CDCA5 mRNA and ERK mRNA in hepatocellular carcinoma tissues was higher than those in the normal hepatic tissues, and the differences were statistically significant(P<0.05). The relative expressions of CDCA5, ERK,CDK1, and cyclin B1 protein in hepatocellular carcinoma tissue were higher than those in the normal hepatic tissues, and the differences were statistically significant(P<0.05). The relative expression of CDCA5 mRNA and ERK mRNA in patients with different tumor diameters, Edmondson grade, Barcelona clinic liver cancer(BCLC) staging, combined portal vein tumor thrombus, and α-fetal protein(AFP) level in hepatocellular carcinoma patients were compared with statistical significance(P<0.05). The expression of CDCA5 and ERK was positively correlated with Edmondson grade Ⅲ-Ⅳ,BCLC stage B-C, portal vein tumor thrombus, and elevated AFP level(P<0.05). Conclusion The promotion of CDK1 and cyclin B1 expression, exacerbating the malignant proliferation of tumor cells, induced by CDCA5 may rely on ERK phosphorylation. It is expected to be a new target for the treatment of stem hepatocellular carcinoma in clinic.
作者
李德新
李飞
赵晓晨
李华
李茂德
兰戴天
安祥
LI Dexin;LI Fei;ZHAO Xiaochen;LI Hua;LI Maode;LAN Daitian;AN Xiang(Department of Hepatobiliary and Pancreatic Surgery,Eastern Hospital,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu 610010,Sichuan,China)
出处
《癌症进展》
2021年第3期264-267,共4页
Oncology Progress
基金
2017年度四川省医学科学院·四川省人民医院临床研究及转化基金(2017LY19)。
关键词
肝细胞癌
细胞分裂周期相关蛋白5
细胞外调节蛋白激酶
hepatocellular carcinoma
cell division cycle associated 5
extracellular regulated protein kinase