【作者】 杨健；

【导师】 王伟林； 方哲平；

【作者基本信息】 浙江大学 ， 外科学， 2011， 硕士

【摘要】 背景：恶性肿瘤的生长、侵袭以及转移机制是目前肿瘤学界探讨的重点,近年来的研究证实了新生血管的形成在肿瘤的生长、转移中起着关键性作用。因此,抑制肿瘤血管生成可抑制肿瘤生长和转移.,所谓抗肿瘤血管生成基因治疗就是向肿瘤或靶细胞周围组织导入血管生成调节因子基因,通过改变肿瘤血管诱导因子和抑制因子之间的平衡来达到治疗肿瘤的目的。目前抗肿瘤血管生成基因治疗主要通过以下3个途径来进行：(1)下调促血管形成因子的表达；(2)诱导血管新生抑制因子的生成；(3)干扰细胞间的信号的传递。肝细胞生长因子的第一个Kringle结构域(the kringle 1 domain of human hepatocyte growth factor, HGFK1),作为一种新的抗血管生成分子,正成为当前恶性肿瘤基因治疗研究中的新宠。但目前对HGFK1与肝癌关系报道相对较少,且意见在有些方面不一致。目的：观察HGFK1在肝细胞癌中的表达,探讨HGFK1与肝细胞癌浸润和转移及预后的关系。方法：收集浙江省台州医院2002年5月～2005年5月经病理学检查证实均为肝细胞癌的58例原发性肝癌患者的手术切除标本,其中男性44例,女性14例,年龄29～72岁,平均54.68岁。根据肝癌细胞分化程度：分高分化组24例(Edmondson分级Ⅰ～Ⅱ级),低分化组34例(Edmondson分级Ⅲ～Ⅳ级)；根据病理诊断证实有无门脉癌栓者：分有门脉癌栓者16例,无门脉癌栓者42例；根据3年有无复发分：复发组的32例,未复发组的26例。计算5年生存率,生存时间从术后第1天算起,截止期为2010年5月30日。采用免疫组化(Envision法)法观察HGFK1在58例肝细胞癌标本中的表达情况。结果：低分化组HGFK1高表达的7例,高表达率20.1%；高分化组高表达14例,高表达率58.3%；2组之间的HGFK1高表达率经比较,有显著差异性(P<0.01)；门脉癌栓形成组HGFK1高表达为4例,高表达率为25%；而无门脉癌栓形成组HGFK1的高表达为24例,高表达率为57.1%,两组之间HGFK1高表达率比较,有显著性差异(P<0.05)；3年复发组HGFK1高表达为9例,高表达率为28.1%,而3年未复发组HGFK1的高表达为19例,高表达率为73.1%,两组之间HGFK1高表达率比较,有显著性差异(P<0.05); HGFK1高表达的患者的5年生存率为43.5%, HGFK1低表达的患者的5年生存率为16.7%,两者相比有统计学差异(P<0.05)。结论：HGFKI的表达与肝细胞癌病理分级及有无门脉癌栓形成相关,与患者年龄、性别、术前AFP水平、肿瘤大小以及Child分级等临床特征无明显关系,可能参与肝癌的发生、发展及转移,可作为肝癌患者预后的重要指标。更多还原

【Abstract】 Background:Malignant tumor growth, invasion and the metastasis of cancer is currently the focus of academic study, recent studies confirmed the formation of new blood vessels in tumor growth and metastasis plays a key role[1-2]. Therefore, inhibition of tumor angiogenesis can inhibit tumor growth and metastasis. The so-called anti-angiogenesis gene therapy is to get the angiogenesis regulatory factor gene into the tumor or target cell’s surrounding tissue, by changing the balance of the tumor angiogenesis factor and inhibitory factor to achieve the purpose of treatment of cancer. Currently gene therapy against tumor angiogenesis mainly through the following three ways:(1)Reduced the expression of angiogenic factors promote; (2)induced angiogenesis inhibitory factor production; (3)interfere with the signal transmission between cells, the kringle 1 domain of human hepatocyte growth factor, HGFK1), as a new anti-angiogenic molecules, is becoming the new darling of the study of the Current cancer gene therapy. But reports on the relationship between HGFK1 and liver cancer is relatively few, and inconsistent in some respects the views. Objective:The expression of HGFK1 in human hepatocellula carcinoma was investigated to explore the relationship of invasion, metastatic of human hepatocellula carcinoma, and prognosis of patients with human hepatocellula carcinoma to HGFK1 expression.Method:Specimens were taken from 58 human hepatocellula carcinoma tissues from Taizhou Hospital. These specimens were obtained from the patients who underwent hepatotomy from January 2002 to March 2005.44 cases were male and 14 females, aged 29～72 years, mean 54.68 years. All cases were confirmed by pathological examination of hepatocellular carcinoma. Hepatoma cell differentiation: well differentiated 24 cases (Edmondson gradeⅠ～Ⅱlevel),34 cases of poorly differentiated (Edmondson grade III-IV level). Pathological diagnosis confirmed 16 cases of portal thrombosis,42 cases of no portal thrombosis. According to 3-year recurrence:32 cases of recurrence,26 cases of no recurrence. Calculated 5-year survival rate. Survival time from counting on postoperative day 1, the deadline for the May 30,2010,SP immunohistochemistry was used to evaluate the expression of HGFK1 in 58 human hepatocellula carcinoma tissues.Results:In poorly differentiated group, HGFK1 high expression in 7 cases, High expression rate is 20.1%(7/34) in high differentiation group, HGFK1 high expression in 14 cases, High expression rate is 58.3%(14/24); the high expression rate of HGFK1 between the 2 groups is significant difference (P<0.01); in portal vein tumor thrombus formation group, HGFK1 high expression in 4 cases, High expression rate is 25%(4/16); in no portal vein tumor thrombus formation group, HGFK1 high expression in 24 cases, high expression rate is 57.1%(24/42). the high expression rate of HGFK1 between the 2 groups is significant difference (P<0.05); in 3-year recurrence group, HGFK1 high expression in 9 cases, high expression rate is 28.1%(9/32), while in the 3-year without recurrence group, HGFK1 high expression in 19 cases, high expression rate is 73.1%(19/26), the high expression rate of HGFKl between the 2 groups is significant difference (P<0.05); the patient with HGFK1 high expression’s 5 year survival rate is 43.5%, the patient with HGFKl low expression’s 5 year survival rate is 16.7%, significantly different between the two (P<0.05).Conclusion:The HGFKl expression is associated with pathological grade of HCC and portal vein tumor thrombus formation,and has not related with age, sex, preoperative AFP level, tumor size and clinical characteristics. The HGFKl expression may be involve in the occurrencer and development and transfer of liver cance, can be used as an important prognostic indicator in patients with liver cancer.更多还原