DNA羟甲基化酶十-十一易位蛋白与5-羟甲基胞嘧啶在食管鳞癌组织的表达及其临床意义  

The expression and clinical significance of ten-eleven translocations and 5-hydroxymethylcytosine in Esophageal cancer

作　　者：薛文华[1] 陈铖鑫 乔镇东 刘东雷[2] 胡亚梅 吴彬[2] 吴恺[2] Xue Wenhua;Chen Chengxin;Qiao Zhendong;Liu Donglei;Hu Yamei;Wu Bin;Wu Kai(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Thoracic Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Outpatient Office,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450052 [2]郑州大学第一附属医院胸外科,郑州450052 [3]郑州大学第一附属医院门诊办公室,郑州450052

出　　处：《中华实验外科杂志》2024年第1期148-151,共4页Chinese Journal of Experimental Surgery

基　　金：河南省中青年卫生健康科技创新优秀青年人才培养项目(YXCC2020055);河南省医学科技攻关项目(SBGJ202002077);河南省自然科学基金项目(202300410460);河南省高等学校重点科研项目(23A320061);河南省中青年卫生健康科技创新优秀青年人才培养项目(YXKC2022060);河南省医学科技攻关计划联合共建项目(LHGJ20200300)。

摘　　要：目的探讨十-十一易位蛋白(TETs)和5-羟甲基胞嘧啶(5hmC)在食管鳞癌组织的表达及临床意义。方法随机选取2020年1月至2022年8月于郑州大学第一附属医院进行手术治疗的食管鳞癌患者癌组织和癌旁组织(距离癌组织2~3 cm)各10例,采用高效液相-质谱联用法(LC-MS/MS)检测5hmC在食管鳞癌中的修饰水平;采用实时荧光定量聚合酶链反应(qRT-PCR)技术检测TETs mRNA在食管鳞癌中的表达;采用蛋白质印迹法(Western blot)检测TETs在食管鳞癌中的蛋白表达水平,组间比较采用t检验。结果食管鳞癌组织中5hmC修饰水平显著高于食管癌癌旁组织[(0.21±0.03)%比(0.05±0.01)%,t=3.095,P<0.01]。TCGA数据库分析,食管癌组织中TET1表达水平显著高于食管癌癌旁组织(1.48±0.08比0.22±0.05,t=5.032,P<0.01);TET2表达水平显著高于食管癌癌旁组织(6.12±0.32比2.86±0.45,t=11.035,P<0.05);TET3表达水平显著高于食管癌癌旁组织(3.69±0.46比2.46±0.55,t=15.339,P<0.05)。RT-qPCR结果表明,食管癌组织中TET1 mRNA表达水平显著高于食管癌癌旁组织(5.93±0.28比2.58±0.15,t=15.854,P<0.05);TET2 mRNA表达水平显著高于食管癌癌旁组织(5.08±0.12比2.82±0.25,t=14.012,P<0.05);TET3 mRNA表达水平显著高于食管癌癌旁组织(4.88±0.28比3.05±0.17,t=12.715,P<0.05)。Western blot结果表明,TET2蛋白表达水平显著高于食管癌癌旁组织(2.86±0.45比1.00±0.00,t=7.895,P<0.01);TET3 mRNA表达水平显著高于食管癌癌旁组织(2.57±0.26比1.00±0.00,t=8.331,P<0.01)。结论食管鳞癌组织中5hmC表达水平高于癌旁组织,癌组织中TET2及TET3 mRNA及蛋白水平均呈高表达。Objective To investigate the expression and clinical significance of ten-eleven translocations(TETs)and 5-hydroxymethylcytosine(5hmC)in esophageal cancer(EC)patients.Methods A total of 10 cases of EC and 10 cases of paracancerous tissues were randomly selected.The level of 5hmC in patients was determined by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS).The mRNA expression of TETs were measured by quantitative real-time PCR(qRT-PCR).The TETs protein expression was detected using Western blotting.Results The level of 5hmC was highly increased in EC patients as compared with paracancerous tissues[(0.21±0.03)%vs.(0.05±0.01)%,t=3.095,P<0.01].Analysis of TCGA database indicated the expression of TET1,TET2 and TET3 in EC tissues was significantly higher than in the paracancerous tissues(1.48±0.08 vs.0.22±0.05,t=5.032,P<0.01;6.12±0.32 vs.2.86±0.45,t=11.035,P<0.05;3.69±0.46 vs.2.46±0.55,t=15.339,P<0.05).The mRNA expression of TET1,TET2 and TET3 in EC tissues was higher than in paracancerous tissues(5.93±0.28 vs.2.58±0.15,t=15.854,P<0.05;5.08±0.12 vs.2.82±0.25,t=14.012,P<0.05;4.88±0.28 vs.3.05±0.17,t=12.715,P<0.05).The protein expression of TET2 and TET3 was largely increased in EC tissues as compared with paracancerous tissues(2.86±0.45 vs.1.00±0.00,t=7.895,P<0.01;2.57±0.26 vs.1.00±0.00,t=8.331,P<0.01).Conclusion The TET2/3 expression and 5hmC levels were significantly higher in EC tissues than in paracancerous tissues.

关 键 词：十-十一易位蛋白 5-羟甲基胞嘧啶 5-甲基胞嘧啶 食管鳞癌 DNA羟甲基化 

分 类 号：R735.1[医药卫生—肿瘤]