TRIM15蛋白在胰腺癌中的表达及作为潜在生物标志物的研究  

Expression of TRIM15 protein in pancreatic cancer and research on its role as a potential biomarker

作　　者：王晓娟 谢方瑜[2] 张巍巍[2] 姜大磊[2] 李文利[2] 付来琳 朱婷婷[2] 王鹤鸣[2] 解祥军[2] WANG Xiaojuan;XIE Fangyu;ZHANG Weiwei;JIANG Dalei;LI Wenli;FU Lailin;ZHU Tingting;WANG Heming;XIE Xiangjun(Clinical College of Weifang Medical College,Weifang 261053,Shandong Province,China;Department of Gastroenterology,Qingdao Municipal Hospital,Qingdao 266011,Shandong Province,China)

机构地区：[1]潍坊医学院临床医学院,山东潍坊261053 [2]青岛市市立医院消化内科,山东青岛266011

出　　处：《解放军医学院学报》2023年第12期1384-1390,1419,共8页Academic Journal of Chinese PLA Medical School

基　　金：青岛市民生科技计划项目(19-6-1-22-nsh)。

摘　　要：背景三结构域蛋白15(tripartite motif 15,TRIM15)广泛参与各种细胞生物学过程,如基因转录调节、细胞生长及分化、信号转导和免疫应答等,TRIM15还与多种恶性肿瘤的生成、进展、侵袭以及药物抵抗等密切相关,但其在胰腺癌发展中的特定功能尚不清楚。目的检测TRIM15在胰腺导管癌(pancreatic ductal adenocarcinoma,PDAC)组织中的表达水平,探讨TRIM15表达与PDAC患者临床病理特征及预后的相关性,预测其影响疾病发展的相关作用机制。方法利用GEO数据库筛选得到与胰腺癌侵袭转移相关的差异基因;采用免疫组织化学染色法检测青岛市市立医院2018年6月-2022年6月收集的72例PDAC标本、40例胰腺癌癌旁标本、5例慢性胰腺炎标本、5例胰腺导管内乳头状黏液性肿瘤标本、6例阳性淋巴结和6例阴性淋巴结标本中TRIM15蛋白的表达水平,并分析临床病理特征;采用单因素及多因素Cox分析识别胰腺癌预后相关危险因素,并利用Kaplan-Meier方法研究TRIM15表达水平对胰腺癌患者总生存时间的影响;最后,通过GO分析和KEGG通路富集分析,确定了TRIM15在信号通路的位置及相关功能。结果GEO数据库筛选得到与胰腺癌侵袭转移相关的4个差异表达基因KLK8、TRIM15、CCL2、FOSB;免疫组织化学染色分析显示,TRIM15在PDAC的表达水平显著高于癌旁组组织(P<0.05)及慢性胰腺炎与胰腺导管内乳头状黏液性肿瘤组织(P<0.05)。TRIM15在PDAC中的高表达与肿瘤分期、肿瘤直径、淋巴结转移、远处脏器转移情况相关(P<0.05)。Cox回归分析显示,TRIM15表达水平是PDAC预后不良的独立因素(P<0.05);Kaplan-Meier生存分析结果显示,TRIM15的阳性表达与PDAC患者低生存率相关(P<0.05)。GO分析和KEGG通路富集分析显示,TRIM15参与胰腺癌细胞间质受体的交互、相关蛋白质的消化与吸收以及局部黏附、PI3KAkt信号传导通路,对胰腺癌的形成和发展有关键影响。结论TRIM15Background Tripartite motif 15(TRIM15)is widely involved in many cellular biological processes,such as gene transcriptional regulation,cell proliferation and differentiation,signal transduction and immune response.It is closely associated with the occurrence and development,invasion and metastasis,and drug tolerance of a variety of malignant tumors.However,the role of TRIM15 in pancreatic cancer is unclear.Objective To investigate the expression of TRIM15 in pancreatic ductal adenocarcinoma(PDAC)tissues and explore the possibility of TRIM15 as a potential biomarker for the diagnosis of pancreatic cancer.Methods GEO database was used to screen the differential genes related to invasion and metastasis of pancreatic cancer;Immunohistochemical staining was used to detect TRIM15 protein expression levels in 72 PDAC samples,40 paracancer samples of pancreatic cancer,5 chronic pancreatitis samples,5 intraductal papillary mucinous tumors of pancreas,6 positive and 6 negative lymph nodes that were collected from Qingdao Municipal Hospital from June 2018 to June 2022,then the clinicopathological features were analyzed.Univariate and multivariate Cox were used to analyze the prognostic risk factors of pancreatic cancer;Kaplan-Meier method was used to analyze the effect of TRIM15 expression level on the overall survival time of pancreatic cancer patients.GO analysis and KEGG pathway enrichment analysis were both used to analyze the signal pathways and main functions of TRIM15.Results Four differentially expressed genes KLK8,TRIM15,CCL2 and FOSB related to pancreatic cancer invasion and metastasis were identified by GEO database;Immunohistochemical staining indicated that the expression level of TRIM15 in PDAC was significantly higher than those in paracancerous tissues(P<0.05),chronic pancreatitis tissues and pancreatic intraductal papillary mucinous tumors of the pancreas(P<0.05).The high expression of TRIM15 in PDAC was correlated with tumor stage,tumor diameter,lymph node metastasis,and distant organ metastasis(all P<0.05

关 键 词：胰腺导管癌 三结构域蛋白家族成员15 免疫组织化学染色 预后 信号通路 

分 类 号：R735.9[医药卫生—肿瘤]