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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) and its prognostic value in patients with liver cancer. Methods The clinical data of 83 patients with hepatocellular carcinoma who underwent liver transplantation were retrospectively analyzed from January 2004 to May 2008 in the Third Affiliated Hospital of Sun Yat-sen University Center for Liver Transplantation. Immunohistochemistry was used to detect HLA-G expression in hepatocellular carcinoma and its adjacent tissues. Kaplan-Meier method was used to calculate the cumulative survival rate and tumor-free survival rate. Log-rank test and Cox regression model were performed respectively Tumor survival rate by single factor and multivariate analysis. Results Of 83 patients with liver cancer, 35 (42.2%) had tumor recurrence. The 1, 3, and 5-year cumulative survival rates were 97.2%, 89.8%, and 43.1% for all cases and 93.6%, 68.9%, and 38.7% for 1,3 and 5 years respectively. The positive rate of HLA-G expression in HCC (68.7%) was significantly higher than that in paracancerous tissues (15.7%, P <0.01). The expression of HLA-G was correlated with tumor diameter, pathological grade and vascular invasion (P <0.05). Univariate analysis showed that the risk factors of tumor-free survival after liver transplantation were HLA-G (P <0.01), tumor diameter (P <0.05), tumor invasion blood vessels (P <0.01) and pathological differentiation P <0.01). The tumor-free survival rate of HLA-G positive group was lower than that of HLA-G negative group (P <0.01). The results of Cox regression model showed that HLA-G expression (P <0.05), tumor invasion (P <0.01) and pathological differentiation (P <0.05) were independent risk factors for postoperative tumor- . Conclusion There is HLA-G expression in HCC tissues. HLA-G expression, tumor invasion of blood vessels and pathological differentiation is an independent risk factor for postoperative tumor-free survival in patients with liver cancer after liver transplantation. The treatment of HLA-G positive patients with intervention and strict screening of liver cancer indications can effectively reduce the recurrence rate of postoperative tumor.