Notch1、Jagged1在肝细胞癌组织中的表达及临床意义

目的探讨Notch1、Jagged1在肝细胞癌组织中的表达及临床意义。方法选择2010年3月～2012年6月手术治疗并经病理证实为肝细胞癌的患者35例,每例患者均取癌组织及癌旁组织（距癌组织2～3 cm处）,其中肝细胞癌组织35例,癌旁肝硬化组织13例,癌旁正常肝组织22例。采用实时荧光定量PCR法检测Notch1mRNA、Jagged1 mRNA在肝细胞癌组织、癌旁肝硬化组织及癌旁正常肝组织中的表达;免疫组织化学染色法检测Notch1、Jagged1蛋白的表达,并分析两种蛋白的表达与肝细胞癌临床病理特征的关系。结果①肝细胞癌组织中Notch1 mRNA、Jagged1 mRNA的表达分别为（4.58±0.77）、（4.96±0.87）,显著高于癌旁正常肝组织,差异有统计学意义（P〈0.05）;与癌旁肝硬化组织（1.16±0.37）、（1.42±0.58）]比较,差异有统计学意义（P〈0.05）;而癌旁正常肝组织与癌旁肝硬化组织比较差异无统计学意义（P〉0.05）。②肝细胞癌组织中,Notch1、Jagged1的阳性表达率分别为71.4%（25/35）、68.6%（24/35）;癌旁正常肝组织中,Notch1、Jagged1的阳性表达率分别为36.4%（8/22）、40.9%（9/22）;癌旁肝硬化组织中,Notch1、Jagged1的阳性表达率分别为30.8%（4/13）、30.8%（4/13）。Notch1、Jagged1的阳性表达率在肝细胞癌组织中明显高于癌旁正常肝组织（χ^2otch1=6.81,χ^2agged1=4.24,P〈0.05）及肝硬化组织（χ^2otch1=6.55,χ^2agged1=5.57,P〈0.05）。Notch1、Jagged1的阳性表达率在癌旁正常肝组织与肝硬化组织间差异无统计学意义（P〉0.05）。Spearman相关分析显示,肝细胞癌组织中Notch1的表达与Jagged1的表达呈正相关（r=0.38,P〈0.05）。③Notch1、Jagged1蛋白的阳性表达率与患者的年龄、性别、肿瘤直径、数目、有无癌栓形成无关（P〉0.05）;与有无淋巴结转移、病理分级密切相关。有淋巴结转移者Notch1、Jagged1阳性表达率高于无淋巴结转移者;低分化癌组织Notch1、Jagged1的阳性表达率明显高于中高分化癌组织,差异均有统计学意义（P〈0.05）。结论 Notch信号通路中Notch1、Jagged1对肝细胞癌的发生发展起促进作用,可为判断临床预后提供参考价值。

Expression and clinical significance of Notch1 and Jagged1 in hepatocellular carcinoma

Objective To explore the expression and clinical significance of Notch1 and Jagged1 in hepatocellular carcinoma. Methods 35 patients of hepatocellular carcinoma treated with operation from March 2010 to June 2012 were selected; carcinoma tissue and para-earcinoma tissue （2-3 cm from carcinoma tissue ） were got in each patient with 35 eases of hepatocellular carcinoma tissues, 13 cases of hepatic cirrhosis tissues, 22 cases of normal hepatic tissues. Real-time PCR was used to measure the expression of Notch1 mRNA and Jagged1 mRNA in hepatocellular carcinoma tissues, hepatic cirrhosis tissues and normal hepatic tissues. Immunohistochemistry was used to measure the expression of Notch1 protein and Jagged1 protein, and the relationship between clinicpathological features and the expression of Notch1 protein, Jagged1 protein were analyzed. Results ①The expression of Notch1 mRNA and Jagged1 mRNA in hepatocellular carcinoma tissues were （4.58±0,77）, （4.96±0.87） respectively, they were higher than those in normal hepatic tissues, the differences were statistically significant （P 〈 0.05）; and the expression of Notch1 mRNA and Jagged1 mRNA in hepatocellular carcinoma tissues were found had statistically significant differences with those in hepatic cirrhosis tissues （1.16±0.37）, （1.42±0.58）] （P 〈 0.05）; the differences of the expression of Notch1 mRNA and Jagged1 mRNA in normal hepatic tissues and hepatic cirrhosis tissues were not statistically significant （P 〉 0.05）.②Positive expression rate of Notch1 and Jagged1 in hepatocellular carcinoma tissues were 71.4% （25/35）, 68.6% （24/35） respectively; positive expression rate of Notch1 and Jagged1 in normal hepatic tissues were 36.4% （8/22）, 40.9% （9/22） respectively; positive expression rate of Notch1 and Jagged1 hepatic cirrhosis tissues were 30.8% （4/13）,30.8% （4/13） respectively. Positive expression rate of Notch1 and Jagged1 in hepatocellular carcinoma tissues were higher than those in normal hepatic tissues（χ^2otch1=6.81,χ^2agged1=4.24,P〈0.05）and hepatic cirrhosis tissues（χ^2otch1=6.55,χ^2agged1=5.57,P〈0.05）.The differences of positive expression rate of Notch1, Jagged1 in in normal hepatic tissues and hepatic cirrhosis tissues were not statistically significant （P 〉 0.05）. Positive correlation of expression rate of Notch1 and Jagged1 was found in hepatocellular carcinoma tissues （r = 0.38, P 〈 0.05）. ③Positive expression rate of Notch1 and Jagged1 protein were found no relationship with age, gender, diameter of tumor, amount, tumor emboli （P 〉 0.05）; closely relationship were found between the positive expression rate of Notch1 and Jagged1 protein with lymphatic metastasis and pathological grading. Positive expression rate of Notch1 and Jagged1 protein in patients with lymphatic metastasis were higher than those in patients without lymphatic metastasis; positive expression rate of Notch1 and Jagged1 protein in patients with poorly differentiated hepatocellular carcinoma tissue were higher than those in patients with high-middle differentiation carcinoma tissue, the differences were statistically significant （P 〈 0.05）. Conclusion Notch1 and Jagged1 play an important role in the carcinogenesis, progression and predicting prognosis of hepatocellular carcinoma.