生长抑制因子4表达水平与肝癌肝移植术后复发转移及预后的关系

目的探讨生长抑制因子4(ING4)表达水平与原发性肝癌(肝癌)肝移植术后复发转移及预后的关系。方法选取2003年5月至2007年12月在江西省人民医院器官移植科实施肝癌肝移植手术的30例患者作为研究对象。组织标本取自手术切除的肝癌组织和相应癌旁1 cm外的癌旁肝组织(PCLT)。采用免疫组织化学(免疫组化)方法对肝癌组织和PCLT中ING4蛋白的表达进行定性检测,比较两者ING4蛋白的阳性表达率及表达强度的差异。采用蛋白质印迹法检测上述两组织ING4蛋白的表达水平。根据蛋白质印迹法结果,计算肝癌组织和PCLT的ING4蛋白表达量之比,以比值0.48为界,将30例患者分为ING4低表达组(15例)和ING4高表达组(15例),分析两组患者临床病理特征、肝癌肝移植术后复发转移和预后情况。结果免疫组化结果显示肝癌组织的ING4阳性表达率为63%(19/30),PCLT为93%(28/30),两者比较差异有统计学意义(P0.05)。肝癌组织的ING4强阳性表达率为27%(8/30),PCLT为63%(19/30),两者比较差异有统计学意义(P0.05)。蛋白质印迹法结果显示肝癌组织的ING4蛋白阳性率为70%(21/30),PCLT为97%(29/30),两者比较差异有统计学意义(P0.05)。PCLT的ING4蛋白表达水平高于肝癌组织(197±31比109±24,P0.05)。30对标本中有25对ING4表达水平在肝癌组织中下调,下调率为83%。在临床病理学特征方面,ING4低表达组和ING4高表达组在肿瘤结节数目(P=0.025)、静脉浸润(P=0.035)、肝外转移(P=0.017)和分化程度(P=0.025)的差异具有统计学意义。ING4高表达组的累计术后复发转移率低于ING4低表达组,生存率高于ING4低表达组(均为P0.05),ING4高表达组中位生存时间长于ING4低表达组(720 d比540 d P0.05)。结论 ING4蛋白水平在肝癌组织中表达下调,且与肝癌肝移植术后复发转移有关,影响肝癌肝移植患者预后。

Relationship between expression of inhibitor of growth 4 and recurrence/metastasis and prognosis of liver transplantation for hepatocellular carcinoma

Objective To investigate the relationship between inhibitor of growth 4 （ING4） expression and recurrence/metastasis and prognosis of liver transplantation for hepatoeellular carcinoma（ HCC ）. Methods Thirty HCC patients who underwent liver transplantation in the Liver Transplantation Center of Jiangxi Province People＇s Hospital from May 2003 to December 2007, were selected as objects. Tissue samples were acquired from HCC tissue and pericarcinomatous liver tissue （PCLT, 1 cm beside HCC tissue）, which were resected by operation. Expression of ING4 protein in HCC tissue and PCLT was quantitatively measured by immunohistochemistry. Positive expression ratio and expression intensity of ING4 were compared between HCC tissue and PCLT. The expression level of ING4 in the tissues was detected by Western blot. According to theresults of Western blot, ratio of ING4 expression between HCC tissue and PCLT was calculated. As ratio of 0. 48 was boundary, 30 patients were divided into ING4 low expression group（ n = 15）and ING4 high expression group （n - 15 ）. Clinical pathological characteristics, recurrence/metastasis and prognosis of liver transplantation for hepatocellular carcinoma were analyzed between two groups. Results The immunohistochemistry result showed that the positive expression ratio of ING4 was respectively 63% （19/30） in HCC tissue ald 93% （28/30） in PCLT, and there was significant difference （P 〈 0. 05 ）. The strong positive expression ratio was 27% （8/30） in HCC tissue and 63% （ 19/30 ） in PCLT, and there was significant difference （P 〈 0. 05）. The Western blot result showed that positive expression ratio of ING4 was 70% （21/30） in HCC and 97% （29/30） in PCLT, and there was significant difference （P 〈0.05）. The expression level of ING4 protein in PCLT was higher than that in HCC tissue （197 -＋ 31 vs. 109 -＋ 24, P 〈 0. 05）. In 30 pairs of samples, the ratio of ING4 protein down-regulation in HCC tissue was 83% （25/30）. In clinical pathological characteristics, there were significant differences in number of tumor nodes （P = 0. 025 ）, vein invasion （ P = 0. 035 ）, extrahepatie metastasis （ P = 0. 017 ） and tumor cell differentiation（ P = O. 025） between ING4 low expression group and ING4 high expression group. Accumulative recurrence/ metastasis rate of ING4 high expression group was lower than that of ING4 low expression group, and survival rate of ING4 high expression group was higher than that of ING4 low expression group （ both in P 〈 0. 05 ）. Median survival time of ING4 high expression group was longer than that of ING4 low expression group （720 d vs. 540 d, P 〈 0. 05 ）. Conclusions The expression level of ING4 protein decreases in HCC tissue. The decrease is related with recurrence/metastasis after liver transplantation for HCC and affects the prognosis of patients.