转谷氨酰胺酶3对胃癌发展和预后的影响  

Effects of transglutaminase 3 on the development and prognosis of gastric cancer

作　　者：钱江 陈俊杰[2] 毛勤生[1] 朱斌 臧伟杰 薛万江[1] Qian Jiang;Chen Junjie;Mao Qinsheng;Zhu Bin;Zang Weijie;Xue Wanjiang(Department of Gastrointestinal Surgery,Affiliated Hospital of Nantong University,Nantong 226001,China;Clinical Medical Research Center of Affiliated Hospital of Nantong University,Nantong 226001,China)

机构地区：[1]南通大学附属医院胃肠外科,南通226001 [2]南通大学附属医院临床医学研究中心,南通226001

出　　处：《中华实验外科杂志》2023年第2期236-238,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82102825、82102720);江苏省自然科学基金(BK20221272)。

摘　　要：目的探讨转谷氨酰胺酶3(TGM3)对胃癌发展和预后的影响。方法收集南通大学附属医院普外科手术治疗的2010年1月至2011年12月的150例及2020年8月10例患者的配对胃癌组织及癌旁组织。采用实时荧光定量聚合酶联反应及免疫组织化学(IHC)检测TGM3在胃癌组织及癌旁组织中的表达水平。分析TGM3蛋白水平与胃癌患者预后的关系。构建TGM3过表达胃癌细胞株,分为空载体组(NC)和TGM3过表达组(TGM3-1、TGM3-2)。利用克隆形成实验、划痕实验和侵袭实验检测TGM3表达对细胞增殖、迁移和侵袭能力的影响。将购自南通大学动物中心的12只4周龄雄性BALB/c裸鼠随机分为3组构建皮下瘤模型,组间比较采用t检验。结果荧光定量聚合酶联反应和IHC结果表明胃癌组织中TGM3的mRNA和蛋白表达均显著低于癌旁组织(荧光定量聚合酶联反应:t=7.091 P<0.01;IHC:χ^(2)=7.061,P<0.01)。生存分析表明,TGM3高表达患者的总生存期长于低表达患者(风险比=0.576,95%可信区间=0.367~0.904,P<0.05)。实验证明TGM3升高可显著抑制胃癌细胞增殖(NC:1226.667±12.014;TGM3-1:311.333±7.024,t=113.900,P<0.01;TGM3-2:337.667±10.599,t=96.110,P<0.01)、迁移(NC:0.477±0.031;TGM3-1:0.260±0.028,t=9.016,P<0.01;TGM3-2:0.223±0.007,t=13.720,P<0.01)和侵袭能力(NC:583.667±13.577;TGM3-1:386.000±8.185,t=21.600,P<0.01;TGM3-2:365.333±10.599,t=21.960,P<0.01),以及抑制裸鼠皮下瘤生长[NC:(0.864±0.071)cm^(3);TGM3-1:(0.353±0.027)cm^(3),t=11.630,P<0.01;TGM3-2:(0.256±0.040)cm^(3),t=12.890,P<0.01]。结论TGM3在胃癌中发挥抑癌作用,可作为预测胃癌患者预后的分子标志物和潜在的治疗靶点。Objective To investigate effects of transglutaminase 3(TGM3)on the development and prognosis of gastric cancer(GC).Methods Paired GC tissues and paracancerous tissues were collected from 150 patients surgically treated from January 2010 to December 2011 and 10 patients in August 2020 at the General Surgery Department of Nantong University Hospital.Quantitative real-time polymerase chain reaction(RT-qPCR)and immunohistochemistry(IHC)were used to detect TGM3 expression levels in GC tissues and paracancerous tissues.The relationship between TGM3 protein levels and prognosis of GC patients was analyzed.Gastric cancer cells overexpressing TGM3 were constructed and divided into empty vector group(NC)and TGM3 overexpressing group(TGM3-1,TGM3-2).Clone formation,scratch and invasion assays were used to detect the effects of TGM3 on cell proliferation,migration and invasion,respectively.A total of 124-week-old male BALB/c nude mice were randomly divided into three groups to construct subcutaneous tumor model,and the differences were compared by t-test.Results The results of RT-qPCR and IHC showed that the protein and mRNA expression of TGM3 in GC tissues was lower than that in normal tissues(RT-qPCR:t=7.091,P<0.01;IHC:χ^(2)=7.061,P<0.01).Survival analysis showed that overall survival was significantly longer in patients with high TGM3 expression than in those with low expression(hazard ratio=0.576,95%confidence interval=0.367-0.904,P<0.05).The experiments demonstrated that TGM3 overexpression significantly inhibited GC cell proliferation(NC:1226.667±12.014;TGM3-1:311.333±7.024,t=113.900,P<0.01;TGM3-2:337.667±10.599,t=96.110,P<0.01),migration(NC:0.477±0.031;TGM3-1:0.260±0.028,t=9.016,P<0.01;TGM3-2:0.223±0.007,t=13.720,P<0.01)and invasive ability(NC:583.667±13.577;TGM3-1:386.000±8.185,t=21.600,P<0.01;TGM3-2:365.333±10.599,t=21.960,P<0.01),and suppressed subcutaneous tumor growth[NC:(0.864±0.071)cm^(3);TGM3-1:(0.353±0.027)cm^(3),t=11.630,P<0.01;TGM3-2:(0.256±0.040)cm^(3),t=12.890,P<0.01].Conclusion TGM3 plays an

关 键 词：胃癌 转谷氨酰胺酶3 预后 

分 类 号：R735.2[医药卫生—肿瘤]