ADAMTS9对甲状腺癌患者预后的影响及其作用机制  

Influence of ADAM metallopeptidase with thrombospondin type 1 motif 9 on the prognosis of patients with thyroid cancer and its mechanism of action

作　　者：曹晓东[1] 项承 CAO Xiaodong;XIANG Cheng(Department of Thyroid and Breast Surgery,Zhoukou Central Hospital,Zhoukou 466000,China)

机构地区：[1]周口市中心医院甲状腺乳腺外科,河南周口466000 [2]浙江大学第二附属医院甲状腺外科

出　　处：《精准医学杂志》2025年第2期153-157,共5页Journal of Precision Medicine

基　　金：国家自然科学基金项目(81701727)。

摘　　要：目的探讨血小板结合蛋白基序的解聚蛋白样金属蛋白酶-9(ADAMTS9)对甲状腺癌(thyroid can-cer,THCA)患者预后的影响及其潜在作用机制。方法从TCGA数据库获取THCA组织中ADAMTS9表达水平及患者临床资料,HPA数据库获取THCA组织中ADAMTS9蛋白表达数据,比较ADAMTS9及其蛋白染色程度、染色强度在正常组织及THCA组织中的表达差异。通过功能富集分析预测ADAMTS9在THCA中可能参与的生物学过程。在Kaplan-Meier Plotter数据库分析ADAMTS9表达水平对THCA患者总体生存时间的影响;通过基因集富集分析方法分析ADAMTS9以及重要预后因子参与THCA的潜在信号通路。结果ADAMTS9在THCA组织中的表达水平显著高于正常组织(t=12.35,P<0.05),且其蛋白染色程度及强度均显著高于正常组织(t=18.68、12.35,P<0.05);功能富集分析显示ADAMTS9主要参与RNA剪接及基因表达调控。ADAMTS9高表达组患者的总体生存期显著长于低表达组(HR=0.22,95%CI=0.06~0.76,P<0.05)。通路分析结果显示ADAMTS9表达水平与钙信号通路评分呈正相关(NES=1.852,P<0.05),与鞘糖脂生物合成通路及柠檬酸盐循环通路评分呈负相关(NES=-1.581、-1.863,P<0.05)。年龄为患者总体生存时间独立预后因子(HR=1.11,95%CI=1.05~1.67,P<0.05),在高龄组THCA患者中柠檬酸盐循环及脂肪酸代谢等能量代谢相关通路显著富集。结论ADAMTS9及其蛋白在THCA组织中均高表达,其高表达有利于患者预后,可能与抑制能量代谢通路相关。此外,ADAMTS9的作用可能在一定程度上抵抗了年龄因素对预后的不利影响。Objective To investigate the influence of ADAM metallopeptidase with thrombospondin type 1 motif 9(ADAMTS9)on the prognosis of patients with thyroid cancer(THCA)and its potential mechanism of action.Methods TCGA database was used to obtain the data on the expression level ofADAMTS9in THCA tissue and the clinical data of patients,and HPA database was used to obtain the data on the protein expression level of ADAMTS9 in THCA tissue.The expression level ofADAMTS9was compared between normal tissue and THCA tissue,as well as the degree and intensity of ADAMTS9 protein staining.A functional enrichment analysis was used to predict the biological processes involvingADAMTS9in THCA.The Kaplan-Meier Plotter database was used to analyze the influence of the expression level ofADAMTS9on the overall survival time of THCA patients,and gene set enrichment analyses were used to explore the potential signaling pathways associated withADAMTS9and important prognostic factors in THCA.Results Compared with normal tissue,THCA tissue showed a significantly higher expression level ofADAMTS9(t=12.35,P<0.05)and significantly higher degree and intensity of ADAMTS9 protein staining(t=18.68,12.35,P<0.05).The functional enrichment analysis showed thatADAMTS9mainly participated in the regulation of RNA slicing and gene expression.The patients with highADAMTS9expression had a significantly longer overall survival time than those with low expression(HR=0.22,95%CI=0.06-0.76,P<0.05).The pathway analysis showed that the expression level ofADAMTS9was positively correlated with calcium signaling pathway score(NES=1.852,P<0.05)and was negatively correlated with glycosphingolipid biosynthesis pathway score and citrate cycle pathway score(NES=-1.581,-1.863,P<0.05).Age(HR=1.11,95%CI=1.05-1.67,P<0.05)was an independent prognostic factor for the overall survival time of patients,and significant enrichment of energy metabolism-related pathways was observed in elderly THCA patients,such as citrate cycle and fatty acid metabolism.Conclusion High mRNA and prote

关 键 词：甲状腺肿瘤 ADAMTS9蛋白质 基因表达 预后 能量代谢 影响因素分析 计算生物学 数据库 遗传学 

分 类 号：R736.1[医药卫生—肿瘤]