CyclinD1在肝细胞癌中的表达及与肝细胞癌患者预后的关系

The relationship between the expression of CyclinD1 in hepatocellular carcinoma and the prognosis of the hepatocellular carcinoma patients

目的探讨CyclinD1在肝细胞癌中的表达及与肝细胞癌患者预后的关系。方法取133例肝细胞癌患者的癌组织(HCCs)及癌旁组织(PTLTs)病理切片,用免疫组化染色技术分析CyclinD1的表达,统计分析CyclinD1表达强度与肝细胞癌患者临床病理因素之间的关系,并以Kaplan-Meier生存曲线及Log-rank法检测不同CyclinD1表达组的生存差异。最后以单因素及多因素Cox回归模型分析影响肝细胞癌患者预后的独立危险因素。结果免疫组化染色结果发现51例肝癌患者的癌组织中CyclinD1表达阳性,表达率为38.3%(51/133),而在癌旁组织中仅有4例CyclinD1表达阳性,表达率为3%(4/133),肝癌组织中Cy-clinD1表达率显著高于癌旁组织(P=0.01)。Mann-WhitneyU检验发现肝癌组织中CyclinD1的高表达与AFP水平(P=0.006)之间呈正相关,且有统计学意义。而CyclinD1表达与性别(P=0.394)、年龄(P=0.232)、肿瘤大小(P=0.842)、肿瘤数目(P=0.479)、包膜(P=0.085)、脉管侵犯(P=0.331)、淋巴结转移(P=0.168)和Edmondson-Steiner病理分级(P=0.521)不相关;Kaplan-Meier生存曲线发现CyclinD1表达强度与患者生存相关,即表达强者预后差(P=0.001);单因素及多因素Cox回归分析发现肿瘤数目、脉管侵犯、CyclinD1表达是影响HCC患者预后的独立危险因素(P值分别为0.003,0.010和0.017)。结论 CyclinD1在肝细胞癌中表达升高,其表达与肝细胞癌患者预后呈负相关,并且是肝细胞肝癌预后的独立危险因素。

Objective To determine CyclinD1 expression in hepatocellular carcinoma （HCC）and paratumorous liver tissues （ PTLTs）, and explore the significance of CyclinD1 in the prognosis of HCC patients. Methods Immunohistochemistry analysis was performed on the sections of paraffin samples in 133 pairs of HCCs and PTLTs to evaluate expression level of CyclinD1. The differences of CyclinD1 expression in HCCs and PTLTs were analyzed with the X^2 test. The correlations between CyclinD1 expression and clinicopathologic factors were analyzed with Mann-Whitney U test. The Kaplan-Meier method and log-rank test were employed to compare the cumulative survival between CyclinD1 negative expression group,weak expression group, expression group, and strong expression group. To reveal the independent factors for prognosis, univariable and muhivariable Cox regression analysis was performed. Results The expression rate of CyclinD1 was significantly higher in tumor tissues （38. 3% ）than that in PTLTs（3% ,P 〈 0.01 ）. The upregulated CyclinD1 expression in HCCs was significantly correlated to serum α- fetoprotein level （P = 0.006 ）. CyclinD1 expression predicts shorter cumulative survivals. Univariable and multivariable Cox regression analysis revealed that the tumor numbers, vascular invasion, and the increased CyclinD1 expression were independent factors for HCC prognosis （ P = 0. 003, 0. 010, 0. 017 respectively ）. Conclusions CyclinD1 expression is upregulated in HCC and is related to shorter cumulative survival, suggesting that CyclinD1 might play an important role in the carcinogenesis of HCC and predict a poor prognosis of HCC natients.