【作者】 张银柱；

【导师】 刘文天；

【作者基本信息】 天津医科大学 ， 内科学， 2008， 硕士

【摘要】 目的:研究表遗传学调控因子组蛋白去乙酰化酶-1（HDAC1）、组蛋白乙酰化酶p300及p21^WAF1蛋白在胃癌组织和癌旁正常黏膜中的表达,探讨它们在胃癌发生、发展中的作用,为胃癌的诊断、治疗和判断预后提供依据。资料和方法:取42例胃癌患者癌灶和相应的癌旁正常黏膜组织标本,用免疫组织化学的方法检测HDAC1、p300和p21^WAF1蛋白表达。经统计分析表达差异和相互关系。结果:1.HDAC1蛋白在胃癌组织和癌旁正常黏膜中的阳性率分别为59.52%（25/42）和35.71%（15/42）,p300蛋白在胃癌组织和癌旁正常黏膜中的阳性率分别为45.24%（19/42）和69.04%（29/42）,p21^WAF1蛋白在胃癌组织和癌旁正常黏膜中的阳性率分别为40.48%（17/42）和64.29%（27/42）。2.胃癌组织中HDAC1、p300和p21^WAF1蛋白的表达水平与癌旁正常黏膜相比均有统计学意义:胃癌组织中HDAC1蛋白的表达明显高于癌旁正常黏膜（P＜0.05）,胃癌组织中p300及p21^WAF1蛋白的表达明显低于癌旁正常黏膜（P＜0.05）。3.HDAC1蛋白的表达与胃癌的分化程度及淋巴结转移相关:低分化癌组织中HDAC1蛋白表达明显高于高、中分化癌（P＜0.05）,胃癌伴淋巴结转移者HDAC1蛋白表达水平明显高于无淋巴结转移者（P＜0.05）。4.p300蛋白的表达水平与胃癌的浸润深度及淋巴结转移相关:侵及浆膜层者p300蛋白表达水平明显低于未及浆膜层者（P＜0.05）,伴淋巴结转移者p300蛋白表达水平明显低于无淋巴结转移者（P＜0.05）。5.p21^WAF1蛋白的表达水平与胃癌的浸润深度及淋巴结转移相关:侵及浆膜层者的p21^WAF1蛋白表达水平明显低于未及浆膜层者（P＜0.05）,伴淋巴结转移者的p21^WAF1蛋白表达水平明显低于无淋巴结转移者（P＜0.05）。6.在胃癌组织中,HDAC1与p21^WAF1蛋白的表达呈负相关（相关系数r=-0.407,P＜0.05）;p300与p21^WAF1蛋白的表达呈正相关（相关系数r=0.323,P＜0.05）;而HDAC1与p300蛋白的表达无相关性（P＞0.05）。7.在癌旁正常黏膜中,HDAC1与p21^WAF1蛋白的表达呈负相关（相关系数r=-0.348,P＜0.05）;p300与p21^WAF1蛋白的表达呈正相关（相关系数r=0.361,P＜0.05）;而HDAC1与p300蛋白的表达无相关性（P＞0.05）。结论:1.胃癌组织中HDAC1蛋白高表达,并与病理分化程度及淋巴结转移相关,提示HDAC1可能有促进胃癌的发生、发展和浸润转移的作用。2.胃癌组织中p300和p21^WAF1蛋白低表达,并与癌的浸润深度及淋巴结转移相关,提示p300与p21^WAF1蛋白表达降低可能是胃癌发生浸润转移的重要原因之一。3.胃癌组织和癌旁正常黏膜中HDAC1和p21^WAF1蛋白的表达均呈负相关,提示HDAC1可能通过组蛋白去乙酰化的作用下调p21^WAF1的表达,导致并促进胃癌的发生发展。4.胃癌组织和癌旁正常黏膜中p300和p21^WAF1蛋白的表达均呈正相关,提示p300可能通过组蛋白乙酰化的作用上调p21^WAF1的表达,抑制胃癌的发生、发展和浸润转移。5.由于p21^WAF1的表达受组蛋白乙酰化相关酶HDAC1、p300的调节,胃癌的发生中HDAC1和p300可能通过对p21^WAF1的调节参与细胞周期的调控。6.HDAC1、p300和p21^WAF1可能作为早期胃癌诊断和预后判断的指标及胃癌治疗的新靶点,对三者的检测作为反映胃癌病理学特点的参考指标具有一定意义。更多还原

【Abstract】 Objectives:To investigate the expression of HDAC1,p300 and p21^WAF1and correlations among them in gastric carcinoma and normal mucosa adjacent to carcinoma,we want to explore their roles in gastric carcinoma and supply theoretical basis for diagnosis, treatment and prognosis of gastric carcinoma.Methods:Immunohistochemistry was performed to detect the expression of HDAC1, p300 and p21^WAF1in 42 specimens of gastric carcinoma and normal mucosa adjacent to carcinoma.All data were analyzed by SPSS 11.5 software.Results:1.The positive rate of expression of HDAC1,p300 and p21^WAF1in gastric carcinoma and normal mucosa adjacent to carcinoma was 59.52%,35.71%;45.24%, 69.04%and 40.48%,64.29%respectively.2.The positive rate of expression of HDAC1 in gastric carcinoma was significantly higher than normal mucosa（P＜0.05）,while the positive rate of expression of p300 and p21^WAF1in gastric carcinoma were statistically lower than normal mucosa（P＜0.05）.3.The positive rate of expression of HDAC1 in poorly-differentiated adenocarcinoma was obviously higher than well-differentiated and moderately differentiated adenocarcinoma（P＜0.05）,the positive rate of expression of HDAC1 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis（P＜0.05）.4.The positive rate of expression of p300 in gastric carcinoma with T3 and T4 infiltrative depth was significantly lower than gastric carcinoma with T1 and T2 infiltrative depth（P＜0.05）,the positive rate of expression of p300 in gastric carcinoma with lymph node metastasis was statistically lower than that without lymph node metastasis（P＜0.05）.5.The positive rate of expression of p21^WAF1in gastric carcinoma with T3 and T4 infiltrative depth was strikingly lower than gastric carcinoma with T1 and T2 infiltrative depth（P＜0.05）,the positive rate of expression of p21^WAF1in gastric carcinoma with lymph node metastasis was statistically lower than that without lymph node metastasis（P＜0.05）.6.In gastric carcinoma,the expression of HDAC1 was negatively correlated with the expression of p21^WAF1（r=-0.407,P＜0.05）,the expression of p300 was positively correlated with the expression of p21^WAF1（r=0.323,P＜0.05）,but there was no correlation between the expression of HDAC1 and p300（P＞0.05）.7.In normal mucosa adjacent to carcinoma,the expression of HDAC1 was negatively correlated with the expression of p21^WAF1（r=-0.348,P＜0.05）,the expression of p300 was positively correlated with the expression of p21^WAF1（r=0.361, P＜0.05）,but there was no correlation between the expression of HDAC1 and p300（P＞0.05）.Conclusions:1.High expression of HDAC1 in gastric carcinoma was observed and it was correlated with the pathologic differentiation degree and lymph node metastasis.Our reasearch suggests that HDAC1 promotes the development,infiltration and lymph node metastasis of gastric carcinoma.2.Low expression of p300 and p21^WAF1in gastric carcinoma was observed and it was correlated with infiltrative depth and lymph node metastasis.It suggests that low expression of p300 and p21^WAF1could be one of the important causes which affected the infiltration and lymph node metastasis of gastric carcinoma.3.The expression of HDAC1 in gastric carcinoma and normal mucosa adjacent to carcinoma was negatively correlated with the expression of p21^WAF1.It shows that HDAC1 may have a inhibitory effect on p21^WAF1by histone deacetylation, then accelerate the development of gastric carcinoma.4.The expression of p300 in gastric carcinoma and normal mucosa adjacent to carcinoma was positively correlated with the expression of p21^WAF1,so p300 may promote the expression of p21^WAF1by histone acetylation,then prevent the development,infiltration and metastasis of gastric carcinoma.5.Because the expression of p21^WAF1was regulated by HDAC1 and p300,HDAC1 and p300 can be involved in cell cycle by regulating the expression of p21^WAF1in the development of gastric carcinoma.6.HDAC1、p300 and p21^WAF1may be the molecule markers of gastric cancer and be used in diagnosis,prognosis and therapy of gastric carcinoma.更多还原