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胃癌组织中DNMT3A1和DNMT3A2的表达及临床意义

Expressions and clinical significance of DNMT3A1 and DNMT3A2 in gastric cancer tissues

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【作者】 崔鹤张爱凤李懿萍郭迪迪霍新颖樊红

【Author】 CUI He;ZHANG Aifeng;LI Yiping;GUO Didi;HUO Xinying;FAN Hong;Department of Forensic Center,Jiangsu Province Hospital,the First Affiliated Hospital of Nanjing Medical University;

【通讯作者】 樊红;

【机构】 南京医科大学第一附属医院江苏省人民医院司法鉴定所东南大学医学院病理病生学系东南大学生命科学研究院南京医科大学附属南京医院肿瘤内科东南大学医学院遗传与发育生物学系

【摘要】 目的探讨胃癌组织中DNA甲基转移酶3A(DNMT3A)两个异构体DNMT3A1和DNMT3A2的表达水平及与临床病理特征和预后的关系。方法收集2005年1月至2012年12月手术切除的96例胃癌组织标本,采用免疫组化SP法检测胃癌组织中DNMT3A1和DNMT3A2的表达,分析两者表达与胃癌临床病理特征(Lauren分型、分化程度、TNM分期、淋巴结转移、远端转移、肿瘤大小、吸烟史和饮酒史)及总生存期(OS)的关系。结果 DNMT3A1和DNMT3A2蛋白在96例胃癌组织中的阳性表达率分别为88. 5%(85/96)和100. 0%(96/96)。DNMT3A1表达与TNM分期、分化程度、淋巴结转移、Lauren分型、远处转移、肿瘤大小、吸烟史和饮酒史均无关(P>0. 05),DNMT3A2表达与分化程度、TNM分期和淋巴结转移有关(P<0. 05)。Cox多因素分析显示,Lauren分型、DNMT3A2表达、肿瘤大小和淋巴结转移是影响胃癌患者OS的独立因素,DNMT3A1表达与OS无关。结论 DNMT3A1和DNMT3A2在胃癌组织表达升高。DNMT3A2高表达与预后不良有关,为胃癌诊治提供新的潜在靶点。

【Abstract】 Objective To investigate the expressions of two isomers of DNA methyltransferase 3A (DNMT3A) including DNMT3A1 and DNMT3A2 in gastric cancer tissues and their relationship with clinicopathological characteristics and prognosis. Methods Ninety-six gastric cancer tissues were obtained from January 2005 to December 2012. Immunohistochemistry SP staining was used to detect the expressions of DNMT3A1 or DNMT3A2. The relationships of their expressions with clinicopathological characteristics (Lauren’s classification,histologic grade,TNM stage,lymph node metastasis,distant metastasis,tumor size,smoking history and drinking history) as well as overall survival (OS) were analyzed. Results The positive expression rates were 88. 5% (85/96) and 100. 0% (96/96) for DNMT3A1 and DNMT3A2 in gastric cancer tissues,respectively. The expression of DNMT3A1 was independent of Lauren’s classification,TNM stage,differentiation,lymph node metastasis,distant metastasis,tumor size,smoking history and drinking history (P>0. 05). DNMT3A2 was related to TNM stage,lymph node metastasis and differentiation of gastric cancer tissues (P<0. 05). Cox multivariate analysis revealed that Lauren’s classification,tumor size,lymph node metastasis and DNMT3A2 expression were independent factors influencing OS,while DNMT3A1 had no influence on OS. Conclusion DNMT3A1 and DNMT3A2 are highly expressed in gastric cancer tissues,and elevated expression of DNMT3A2 is significantly related with poor prognosis of gastric cancer patients. These findings provide a potential therapeutic target for gastric cancer that may be further investigated.

【基金】 国家自然科学基金资助项目(81672414,81472548,81702789)
  • 【文献出处】 临床肿瘤学杂志 ,Chinese Clinical Oncology , 编辑部邮箱 ,2018年11期
  • 【分类号】R735.2
  • 【被引频次】2
  • 【下载频次】139
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