肝癌白细胞抗原-G的表达及其在肝癌肝移植预后中的价值

Expression of Human Leukocyte Antigen-G and Its Prognosis Value for Liver Transplant Patients with Hepatocellular Carcinoma

目的探讨人类白细胞抗原-G(human leukocyte antigen-G,HLA-G)在肝细胞肝癌组织中的表达及其在肝癌肝移植患者预后中的价值。方法回顾性分析2004年1月至2008年5月期间中山大学附属第三医院肝移植中心收治的83例肝癌肝移植患者的临床资料。应用免疫组化方法检测肝细胞肝癌组织及其癌旁组织中HLA-G的表达情况,应用Kaplan-Meier法计算累积生存率和无瘤生存率,采用log-rank检验和Cox回归模型分别进行无瘤生存率单因素和多因素分析。结果 83例肝癌肝移植患者中,35例(42.2%)肿瘤复发。全部病例1、3和5年累积生存率分别为97.2%、89.8%和43.1%,1、3和5年无瘤生存率分别为93.6%、68.9%和38.7%。肝癌组织中HLA-G表达阳性率(68.7%)明显高于癌旁组织(15.7%,P<0.01)。HLA-G的表达与肿瘤直径、病理分级和血管侵犯有关(P<0.05)。单因素分析显示,影响肝癌肝移植术后无瘤生存率的危险因素有HLA-G表达(P<0.01)、肿瘤直径(P<0.05)、肿瘤侵犯血管(P<0.01)及病理分化程度(P<0.01)。HLA-G表达阳性组移植后的无瘤生存率低于HLA-G表达阴性组(P<0.01)。Cox风险回归模型结果表明,HLA-G表达(P<0.05)、肿瘤侵犯血管(P<0.01)及病理分化程度(P<0.05)是影响肝癌肝移植患者术后无瘤生存率的独立危险因素。结论肝癌组织存在HLA-G表达。HLA-G表达、肿瘤侵犯血管及病理分化程度是影响肝癌肝移植患者术后无瘤生存率的独立危险因素。对HLA-G表达阳性患者采取干预治疗及严格筛选肝癌肝移植的适应证可有效降低术后肿瘤的复发率。

Objective To investigate the expression of human leukocyte antigen-G （HLA-G） in hepatocellular carcinoma （HCC） tissues, and to evaluate the prognosis of patients after liver transplantation. Methods The clinical data of 83 patients with HCC who underwent liver transplantation from January 2004 to May 2008 in the Liver Transplan- tation Center of the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, The expression of HLA-G in HCC tissues was detected by using immunohistochemical analysis. The Kaplan-Meier method was used to evaluate the cumulative survival rate and tumor-free survival rate. Log-rank test and Cox regression model were used to analyze the single and muti-factor for tumor-free survival rate, respectively. Results Among the 83 patients, therewere tumor recurrence in 35 patients （42.2%）. The 1-year, 3-year, and 5-year of cumulative survival rate was 97.2%, 89.8%, and 43.1%, respectively. The 1-year, 3-year, and 5-year of tumor-free survival rate was 93.6%, 68.9%, and 38.7%, respectively. The positive rate （68.7%） of HLA-G expression in HCC tissues was significantly higher than that in paracancerous tissues （15.7%）, P 〈 0. 01. A significant association was found between expression of HLA-G and tumor size, vascular invasion, and pathology differentiation （P〈0. 05）. Single factor analysis showed that the expres- sion ofHLA-G （P〈0. 01）, tumor size （P〈0. 05）, vascular invasion （P〈0.01）, and pathology differentiation （P〈0. 01） effected on tumor-free survival rates of HCC patients after liver transplantation. The tumor-free survival rate in positive expression of HLA-G group was significantly lower than that in negative expression of HLA-G group （P〈 0. 01）. Cox regression model analysis showed that the expression of HLA-G （P〈 0. 05）, vascular invasion （P〈 0. 01）, and pathol- ogy differentiation （P 〈 0. 05） were independent risk factors that affected the tumor-free survival rate of HCC patients after liver transplantation. Conclusions There is expression of HLA-G in HCC tissues. The independent risk factors that affecting the tumor-free survival rate of HCC patients after liver transplantation include the expression of HLA-G, vascular invasion, and pathological differentiation. Taking interferential measures for patients with positive expression of HLA-G and strict selection of indication of liver transplantation for HCC can reduce the recurrence rate of tumor.