核糖核苷酸还原酶亚基RRM1、RRM2和RRM2B表达对肝细胞癌患者预后的影响  

Prognostic significance of protein expressions of ribonueleotide reductase subunits RRM1, RRM2 and RRM2B in hepatocellular carcinoma

作　　者：田华[1] 李红[1] 张立行[1] 葛超[1] 陈陶阳[2] 谢海洋[3] 崔英[4] 李锦军[1] 

机构地区：[1]上海交通大学医学院附属仁济医院上海市肿瘤研究所癌基因与相关基因国家重点实验室,上海200032 [2]启东肝癌防治研究所,江苏启东226200 [3]浙江大学医学院第一附属医院肝胆胰外科,浙江杭州310003 [4]广西肿瘤防治研究所,广西南宁530021

出　　处：《肿瘤》2014年第5期458-463,共6页Tumor

基　　金：高等学校博士学科点专项科研基金(编号:20110073120105);上海市自然科学基金(编号:12ZR1430000);国家重点实验室自主研究课题(编号:91-14-09)

摘　　要：目的 :检测核糖核苷酸还原酶(ribonueleotide reductase,RR)亚基RRM1、RRM2和RRM2B蛋白在肝细胞癌中的表达情况,并探讨3种蛋白表达对肝细胞癌患者预后的影响及相关性。方法 :收集原发性肝细胞癌组织197例,采用免疫组织化学法检测RRM1、RRM2和RRM2B蛋白在肝细胞癌组织中的表达水平。应用Spearman相关系数两两分析RRM1、RRM2和RRM2B蛋白表达与各临床病理特征参数之间的关系,KaplanMeier法计算生存率,log-rank检验进行预后的单因素分析,COX比例回归模型进行预后的多因素分析,并计算风险比(hazard ratio,HR)。结果 :阳性染色的RRM1、RRM2和RRM2B主要定位于肝癌细胞质中,RRM1和RRM2蛋白的表达水平与肝细胞癌患者预后均无明显相关性(P>0.05);而RRM2B蛋白高表达的肝癌患者术后生存时间明显长于低表达者(P<0.05)。结论 :RRM2B蛋白表达水平是影响肝细胞癌的独立预后因素。Objective： To explore the effect of protein expressions of ribonueleotide reductase （RR） subunits RRM1, RRM2 and RRM2B on the prognosis of hepatocellular carcinoma （HCC） and their potential relationships with the prognosis of HCC patients. Methods： One hundred and ninety-seven primary HCC tissues were subjected to detect the protein expressions of RRM1, RRM2 and RRM2B by immunohistochemistry. Correlations between RRM1, RRM2 and RRM2B protein expressions and clinicopathological parameters were analyzed by Spearman correlation coefficient. Survival rates were estimated by Kaplan-Meier method. Univariate analysis was performed by log-rank test. COX regression model was used to perform multivariate analysis and hazard ratio （HR） calculation. Results： Positive immunohistochemical stainings of RRM1, RRM2 and RRM2B proteins were mainly located in the cytoplasm of HCC cells. The expressions of RRM1 and RRM2 were not associated with prognosis of HCC patients （P 〉 0.05）; however, the Kaplan-Meier survival analysis demonstrated that the survival time of HCC patients with high expression of RRM2B was longer than those with low expression （P 〈 0.05）. Conclusion： Higher RRM2B protein level in HCC tissues may be a potential independent marker of good prognosis of HCC patients.

关 键 词：癌  肝细胞 核糖核苷酸酶类 免疫组织化学 预后 

分 类 号：R735.7[医药卫生—肿瘤]