婆罗双树样基因4在原发性肝细胞癌中的表达及其与上皮间质转化的关系

Expression of sal-like 4 in primary hepatocellular carcinoma and its association with transition

目的探讨婆罗双树样基因4（SALL4）在原发性肝细胞癌（HCC）组织中的表达及其与上皮间质转化（EMT）和临床病理因素之间的联系。方法采用免疫组织化学和核酸分子原位杂交技术检测SALL4、上皮钙黏蛋白（E-cadherin）、波形蛋白（vimentin）和SnarlmRNA在72例HCC、2例胚胎肝、2例正常成人肝组织中的表达。结果胚胎肝组织肝母细胞SALL4强阳性，原始造血细胞阴性，正常成人肝组织肝细胞和胆管上皮SALIA阴性，HCC中SALL4阳性率为47．2％（34／72），呈局灶性核阳性，有镜下微血管癌栓和门静脉癌栓、血清甲胎蛋白≥350ng／ml、UICC分期Ⅲ＋Ⅳ期、〈46岁的HCC组SALL4阳性强度均高于无镜下微血管癌栓和门静脉癌栓、血清甲胎蛋白〈350ng／ml、UICC分期Ⅰ＋Ⅱ期、≥46岁组，SALL4阳性HCC患者术后无瘤生存率、总体生存率均低于SALL4阴性者垆〈0．05），60％（21／35）的HCC组织微血管癌栓SALL4呈阳性表达。SALL4的阳性率与E-cadherin呈负相关（r=-0．434，P〈0．01），与Vimentin和Snat正相关（Vimentin：r=0．516，P〈0．01；Snail：r=0．571，P〈0．01）。结论原发性HCC中SALL4蛋白的表达对上皮间质转化有重要影响，可为肝癌的侵袭、转移研究和患者的预后判断提供帮助。

Objective To investigate the expression of sal-like 4 （SALL4） in tissues of primary hepatocellular carcinoma （HCC） and its association with epithelial-mesenchymal transition （EMT） and clinicopathological characteristics. Methods Immunohistochemistry and nucleic acid in situ hybridization were used to measure the mRNA expression of SALL4, epithelial cadherin （E-cadherin）, vimentin, and Snail in 72 HCC samples, 2 fetal liver samples, and 2 normal adult liver tissue samples. Results Strong expression of SALIA was observed in hepatoblasts in fetal liver, but SALL4 expression was not observed in primitive hematopoietic cells and normal adult hepatocytes or biliary epithelial cells. In the HCC samples, the positive rate of SALL4 was 47.2% （34/72）, showing focal positive nuclear staining. The HCC patients with microscopic microvascular tumor thrombus and portal vein tumor thrombus, a serum alpha-fetoprotein level of ≥ 350 ng/ml, International Union Against Cancer （UICC） stage III＋IV, and an age of 〈 46 years showed higher positive expression of SALL4 than those with no microscopic microvascular tumor thrombus or portal vein tumor thrombus, a serum alpha-fetoprotein level of〈 350 ng/ml, UICC stage I＋II, and an age of ≥ 46 years. The HCC patients with positive SALIA showed lower postoperative disease-free survival rate and overall survival rate than those with negative SALL4 （P 〈 0.05）. Sixty percent of the patients with microvascular tumor thrombus （21/35） showed positive expression of SALL4. The positive rate of SALL4 was negatively correlated with E-cadherin （r = -0.434, P 〈 0.01）, but positively correlated with vimentin and Snail（vimentin：r=0.516,P〈0.01;Snail：r=0.571,P〈0.01）.Conelusion In patients with primary HCC, the expression of SALIA greatly affects EMT, which helps with the research on invasion and metastasis of liver cancer and prognostic evaluation.