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作 者:王秀茹[1] 刘文天[2] 张秋瓒[3] 乔丽葵[3] 张淑贤[3]
机构地区:[1]天津医科大学总医院,在读研究生天津市300052 [2]天津医科大学总医院消化科 [3]天津医科大学第四中心临床学院
出 处:《中国肿瘤临床》2012年第1期5-9,共5页Chinese Journal of Clinical Oncology
摘 要:目的:探讨HDAC6与P21^(WAF1)在胃癌发生、发展中的作用及其相关性,为胃癌的早期诊断、治疗和判断预后提供依据。方法:应用SP免疫组化法分别检测40例胃癌、30例癌前病变组及32例正常胃黏膜组中H)AC6及P21^(WAF1)蛋白的阳性表达情况。结果:HDAC6组织表达阳性率在胃癌,癌前病变及正常对照组依次降低,分别为65.0%,43.3%,15.6%(P<0.01),P21^(WAF1)组织表达阳性率在胃癌,癌前病变及正常对照组依次升高,分别为45.0%,63.3%和81.3%(P<0.01)。HDAC6的表达在分化程度越低、分期越高和淋巴结转移胃癌组织中显著升高(P<0.05);P21^(WAF1)蛋白阳性表达则相反,在分化程度越低、分期越高和淋巴结转移胃癌组织中显著降低(P<0.05)。胃癌组织中HDAC6与P21^(WAF1)的表达呈负相关(r-0.495,P<0.01);癌前病变、黏膜组织中HDAC6与P21^(WAF1)的表达呈负相关(r=-0.451,P<0.05)。结论:HDAC6与P21WAF1的异常表达可能与促进胃癌的发生、发展和浸润转移有关。HDAC6可能通过下调P21^(WAF1)的表达,导致并促进胃癌的发生发展。HDAC6和P21^(WAF1)可能作为胃癌诊断和预后判断的指标及胃癌治疗的新靶点。Objective: The current paper aims to investigate the HDAC6 and p21^WAF1 expression, as well as their correlations, in gastric carcinoma and normal mucosa adjacent to carcinoma, The roles of these proteins in gastric carcinoma were also investigated. Methods: Immunohistochemistry was performed to detect the HDAC6 and p21^WAF1 expression in 40 specimens of gastric carcinoma, 30 specimens of precancerous lesions ( chronic atrophic gastritis with intestinal metaplasia ), and 32 specimens of normal mucosa adjacent to carcinoma. Results: The expression of HDAC6 in gastric carcinoma, precancerous lesions, and normal mucosa was 65.0%, 43.3%, and 12.5%, respectively. Meanwhile, the positive rates of p21^WAF1 in gastric carcinoma, precancerous lesions, and normal mucosa were 45.0%, 63.3%, and 81.3%, respectively. A significant difference among the expression of HDAC6 and p21^WAF1 in the three groups ( P 〈 0.01 ) was observed. In gastric carcinoma, the HDAC6 expression significantly increased in stage III or IV tumors ( P 〈 0.05 ), positive lymph-node metastasis, and poorly differentiated adenocarcinoma ( P 〈 0.05 ). On the contrary, the p21^WAF1 expression significantly de- creased in stage III or IV tumors ( P 〈 0.05 ), positive lymph-node metastasis, and poorly differentiated adenocarcinoma ( P 〈 0.05 ). A negative correlation was found between the HDAC6 and p21 p21^WAF1 expression in gastric carcinoma ( r = -0.495; P 〈 0.01 ) and precancerous lesions ( r = -0.451; P 〈 0.05 ). Conclusion: HDAC6 may have an inhibitory effect on p21^WAF1 and may promote the development, infiltration, and metastasis of gastric carcinoma. HDAC6 and p21^WAF1 are possible molecular markers of gastric cancer and may be used in the diagnosis and protmosis and as theraneutic targets of gastric carcinoma.
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