山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (4): 14-23.doi: 10.6040/j.issn.1671-7554.0.2024.0125
• 临床医学 • 上一篇
刘爱静1,李雁儒1,高惠茹1,段伟丽1,李培龙1,李娟1,杜鲁涛2,王传新1
LIU Aijing1, LI Yanru1, GAO Huiru1, DUAN Weili1, LI Peilong1, LI Juan1, DU Lutao2, WANG Chuanxin1
摘要: 目的 评估自噬相关蛋白5(autophagy-related protein 5, ATG5)在结肠癌中的表达及其与临床病理特征的关系,分析ATG5对结肠癌细胞迁移及侵袭能力的影响。 方法 运用在线分析工具cProsite分析ATG5 mRNA以及ATG5蛋白在结肠癌组织及癌旁正常组织中的表达水平。使用Kaplan-Meier Plotter分析ATG5表达水平对结肠癌患者预后的影响。免疫组织化学法检测100例结肠癌组织中ATG5表达,χ2和Fishers检验分析ATG5表达水平与临床病理特征的相关性。转染质粒或小干扰过表达或敲低ATG5后,Western blotting检测转染效率及自噬相关标记物微管相关蛋白轻链3(microtubule-associated protein light chain 3, LC3)的变化,Transwell实验评估过表达或敲低ATG5后结肠癌细胞的迁移及侵袭能力。使用LinkedOmics数据库分析结肠癌中与ATG5相关的差异表达基因,并进行基因本体(gene ontology, GO)分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)分析。 结果 结肠癌组织中ATG5 mRNA及蛋白的表达水平均低于癌旁正常组织(P<0.001)。低表达ATG5的结肠癌患者无复发生存期明显短于高表达ATG5的结肠癌患者(P<0.001)。免疫组化结果表明,结肠癌组织中ATG5的表达水平与淋巴结转移相关,低表达ATG5的结肠癌患者更容易发生淋巴结转移(P=0.027)。Western blotting及Transwell实验显示在SW1116细胞中过表达ATG5后,LC3Ⅱ/LC3Ⅰ增加,细胞的迁移侵袭能力减弱(PATG5=0.001;PLC3Ⅱ/LC3Ⅰ=0.04;P迁移<0.001,P侵袭<0.001);反之,在DLD1细胞中敲低ATG5后,LC3Ⅱ/LC3Ⅰ降低,细胞的迁移侵袭能力增加(PATG5#1=0.021,PATG5#2<0.001;PLC3Ⅱ/LC3Ⅰ#1=0.013,PLC3Ⅱ/LC3Ⅰ#2=0.02;P迁移<0.001,P侵袭<0.001)。ATG5相关的差异表达基因富集分析结果显示,结肠癌中ATG5可能通过影响DNA损伤反应、染色质重排及Notch信号通路等途径影响结肠癌的转移。 结论 ATG5在结肠癌中低表达,并与患者淋巴结转移及预后显著相关,结肠癌细胞中ATG5能够增加细胞自噬水平并抑制细胞侵袭转移,提示ATG5及其调控的自噬过程可能成为结肠癌临床治疗的新靶点。
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