【作者】 王彬；

【导师】 庞志刚；

【作者基本信息】 郑州大学 ， 外科学， 2011， 硕士

【摘要】 背景和目的：肝细胞性肝癌(Hepatecellular carcmoma, HCC)以下简称肝癌是我国常见的消化系肿瘤,既使行根治性切除术5年复发率仍高达61%,术后3年是复发的高峰期,而转移复发是治疗失败和患者死亡的主要原因,因此,研究肝癌复发转移机制,成为21世纪专家学者们研究的热点课题。Kai1/cd82蛋白是跨膜4超家族(TM4SF)成员,定位于体内大多数组织的细胞膜,参与细胞与细胞及细胞与胞外基质的相互黏附,对维持组织塑型有一定作用。研究表明Kai1/cd82具有抑制肝癌侵袭转移作用,而其表达减低或缺失是进展期肝癌的标志。随着科技的进步,彩超、螺旋CT、DSA等先进仪器逐渐普及,早期肝癌的检出率大大提高,能行肝癌根治术的病人越来越多。通过临床观察,同样行肝癌根治术,病人的预后有很大差别,有的病人术后很快发生复发转移,有的病人却能长期无瘤存活,且复发早的病人,病情进展很快,如果能发现一种方法能有效评估肝癌根治术后复发转移潜能,进而根据疾病进程进行个体化干预治疗,无疑对提高肝癌病人的预后,降低致死率具有积极意义。那么Kai1/cd82低表达作为进展期肝癌的标志,对肝癌根治术后复发转移潜能有无关系呢?本课题就这一疑问展开。方法：采用经典的免疫组化方法,检测2005年5月-2010年3月间郑大二附院行肝癌根治术标本120例,行姑息手术标本42例,以及正常肝组织11例标本中Kai1/cd82蛋白表达,半定量评分法判定。1)比较三者间的表达差异。2)根据收集到的肝癌根治术病人术后的回访材料(参考AFP、CT、及肝动脉造影结果)以3年为期限,分为三年内复发组(55例)、三年内无瘤存活组(65例),比较两组间Kai1/cd82蛋白的表达差异。然后,比较三年内复发组与行姑息手术组间Kai1/cd82蛋白的表达差异,检验Kai1/cd82蛋白表达与肝癌根治术后复发转移潜能的关系。3)根据临床、病理分型将行肝癌根治术组的标本依次分组,揭示各组间的表达差异,进一步验证Kai1/cd82蛋白表达预测肝癌根治术后转移复发潜能的效力。结果：1)正常肝组织Kai1/cd82蛋白的表达缺失率、表达减低率、表达正常率依次为0%(0/11)、18.2%(2/11)、81.8%(9/11)；行肝癌根治术标本Kai1/cd82蛋白的表达缺失率、表达减低率、表达正常率依次为30%(36/120)、20%(24/120)、50%(60/120)；行肝癌姑息术标本Kai1/cd82蛋白的表达缺失率、表达减低率、表达正常率依次为45.2%(19/42)、28.6%(12/42)、26.2%(11/42)。应用两组有序变量秩和检验,将三组间表达行两两比较,差别均有统计学意义。2)肝癌根治术后三年内复发组标本的Kail/cd82蛋白的表达缺失率、表达减低率、表达正常率依次为41.8%(23/55)、27.3%(15/55)、30.9%(17/55)肝癌根治术后三年内无瘤存活组标本Kail/cd82蛋白的表达缺失率、表达减低率、表达正常率依次为20%(13/65)、13.8%(9/65)、66.2%(43/65)。应用两组有序变量秩和检验,两组间差别有统计意义,然后将肝癌根治术后三年内复发组标本和行肝癌姑息术标本的Kai1/cd82蛋白表达进行比较,两者差别无统计学意义。3)将肝癌根治术组标本根据临床、病理分型依次分组,进行各组间比较。Kai1/cd82蛋白表达在单结节肝癌与多结节肝癌之间,在有完整包膜和无完整包膜之间,在高分化肝癌、中分化肝癌、低分化肝癌之间、在有微血管侵犯和无微血管侵犯之间的差别均有统计学意义。而在肿瘤直径>5cm和肿瘤直径<5cm之间的差别无统计学意义。结论：1) Kai1/cd82蛋白低表达是进展期(侵袭转移)肝癌的标志。2) Kai1/cd82蛋白表达可用于评估肝癌根治术后复发转移潜能。更多还原

【Abstract】 Background and purpose:Hepatocellular carcinoma which shortened form is HCC is the common tumors of the digestive system in our country. Even with radical surgery in following 5 years recurrence ratio still throws up to 61 percent. And the first following three years is the fastigium. Transfer and recurrence is the primary reason of treatment failure and death.Therefore Studying recurrent mechanism of HCC metastasis and recurrent becomes hotspot of experts in the 21 century.Kail/cd82 protein is a family member of TM4SF which is located in the body of most organizations cell membranes and participates in mutual adhesion among cells and among cells and extracellular, which has certain effect in maintaining tissue styling. Studies have already shown that Kai1/ cd82 can inhibit HCC transfer and recurrence and the reduction or the loss of its expression is a symbol of advanced HCC.With the progress of science and technology, advanced inspection instrument such as Color dopplar ultra-sound, spiral CT, and DSA become popular, early detection rate of hepatocellular carcinoma increase greatly, and more and more patients can receive radical hepatocellular carcinoma cure. Through clinical observation, we find that though undergoing the same cure, the patients’prognosis will be great different. Some patients rapidly relapse and metastasis, some patients can survive with disease-free and patients who recrudesce early also recrudesce faster. If we can find a method which can effectively evaluate possibility of HCC recurrence after radical surgery, then according to disease process we can undertake personalized intervention which undoubtedly has positive significance in improving patient’s prognosis and reducing mortality. So does lower Kai1/cd82 expression as advanced HCC logo has relation with transfer and recurrence potential of HCC after radical surgery? This problem is the heart of this paper.Methods:By using classical immunohistochemical method, I checked 120 specimen of radical HCC surgery and 42 specimen who had underwent palliative surgical and 11 specimen with normal liver tissue with time range from May 2005 to March 2010.from the second subsidiary hospital of Zhengzhou university. using half quantitative grading method to judge the kai1/cd82 protein expression. Firstly, I have compared the expression difference among the three types.Secondly,according to the collected return postoperative materials of patients who underwent radical HCC surgery (referencing AFP, CT, and Hepatic artery angiography results),taking 3 years as a term, the patients were divided into 3-years recurrence group (55 cases)and 3-years disease-free survival group (65).I compare Kai1/cd82 expression differences between the two groups and I compare Kai1/cd82 expression differences between 3-years recurrence group and palliative surgical group. Through statistic analysis, we test the relationship between Kai1/cd82 protein expression and recrudescence potential after HCC radical surgery.According to the clinical and pathologic classification, I have further divided the specimen of radical HCC surgery group into different groups to reveal the expression differences and further test the effect of predicting recurrence potential after radical HCC surgey by Kai1/cd82 expression.Results:1) The loss、reduction and normal Kai1/cd82 protein expression rate are 0% (0/11)、18.2%(2/11).81.8%(9/11) in the normal liver tissue group, respectively; and the numbers become 30%(36/120)、20%(24/120)、50%(60/120) in the radical HCC surgery group, respectively; the numbers become 45.2%(19/42).28.6% (12/42)、26.2%(11/42) in the palliative surgery group, respectively. By using ordinal variable rank sum test, the differences between the three groups are statistic significant.2) the loss expression, reduce expression and normal expression of Kai1/cd82 protein for group in which members relapse within 3 years after radical HCC surgery is 41.8% (23/55),27.3% (15/55),30.9%(17/55),respectively. and the value for the survival group without tumor is 20%(13/65 percent),13.8% (9/65),66.2% (43/65),respectively. The ordered variable rank sum test show that the difference between the two groups is statistically significant and the difference of Kail/cd82protein expressions between the 3-years relapse group and radical HCC surgery group has no statistics significance.3) The specimen of radical HCC surgery group were divided into different subgroups based on clinical and pathological classification. I compare the difference between the subgroups and find that the Kail/cd82 protein expression difference is statistics significant between the subgroup with complete envelope and the subgroup without complete envelope. The same can be find among the LDD、MDD、HDD subgroups and so does between the subgroup with microvascular invasion and the subgroup without. While the difference between the tumor diameter> 5cm subgroup and the tumor diameter< 5cm subgroups has no statistical significance.Conclusion:1) Kai1/cd82 protein lower expression is symbol of advanced hepatocellular carcinoma (invasion and metastasis).2) Kail/cd82 protein expression can be used to assess relapse and metastasis potential after radicial HCC surgery.更多还原