E3泛素连接酶TRIM59 在肺癌肿瘤相关巨噬细胞中的表达及临床意义  

Expression and clinical implications of E3 ubiquitin ligase TRIM59 in tumor-associated macrophages in lung cancer

作　　者：范静芝 耿彪 付相君 赵文英 FAN Jingzhi;GENG Biao;FU Xiangjun;ZHAO Wenying(Department of Oncology,The First Affiliated Hospital of Wannan Medical College,Wuhu 241001,China)

机构地区：[1]皖南医学院第一附属医院弋矶山医院肿瘤内科,安徽芜湖241001 [2]皖南医学院第一附属医院弋矶山医院呼吸内科,安徽芜湖241001

出　　处：《皖南医学院学报》2022年第6期535-539,共5页Journal of Wannan Medical College

基　　金：安徽省自然科学基金项目(2008085QH351)。

摘　　要：目的:探讨E3泛素连接酶TRIM59在肺癌肿瘤相关巨噬细胞(TAMs)中的表达水平与临床病理参数的关系以及对患者预后的影响。方法:采用多重荧光免疫组化技术(mIHC)检测E3泛素连接酶TRIM59在肺癌TAMs中的表达水平。根据E3泛素连接酶TRIM59在肺癌TAMs中的表达水平及平均荧光强度(MFIs)评分,统计分析E3泛素连接酶TRIM59的表达与临床病理参数(如肿瘤大小、肿瘤分化程度、淋巴结转移、TNM分期)及患者预后的关系。体外通过上调或下调巨噬细胞(THP-1源性巨噬细胞)中TRIM59的表达水平来进一步验证TAMs中TRIM59的表达水平对肺癌细胞功能的影响。结果:mIHC结果显示,与癌旁组织中的巨噬细胞相比,TAMs中E3泛素连接酶TRIM59的表达水平显著上调,并且TAMs中E3泛素连接酶TRIM59高表达与淋巴结转移、肿瘤分期、远处器官转移有关(P<0.05)。生存分析显示,TAMs中E3泛素连接酶TRIM59表达水平升高,则患者的预后结果较差(P<0.001)。Transwell实验和细胞克隆形成实验表明,巨噬细胞过表达TRIM59促进了肿瘤细胞的侵袭和增殖(P<0.01),与此相反,抑制巨噬细胞TRIM59的表达,则遏制肿瘤细胞的侵袭和增殖(P<0.01)。结论:E3泛素连接酶TRIM59在肺癌TAMs中的表达水平升高,其表达水平与临床病理参数有关。TAMs中TRIM59的表达水平升高则患者的预后较差。TAMs中TRIM59的表达水平升高促进了肿瘤细胞的侵袭和增殖能力。Objective:To investigate the relationship between expression level of E3 ubiquitin ligase TRIM59 in tumor-associated macrophages(TAMs)of lung cancer and clinicopathological parameters and its impact on the prognosis of the patients.Methods:Multiplex IHC(mIHC)was used to detect the expression level of E3 ubiquitin ligase TRIM59 in the TAMs of lung cancer tissues.The relationship between expression of E3 ubiquitin ligase TRIM59 and clinicopathological parameters(such as tumor size,degree of tumor differentiation,lymph node metastasis,TNM staging)and prognosis of the patient was statistically analyzed according to the expression level and mean fluorescence intensity(MFIs)score of E3 ubiquitin ligase TRIM59 in TAMs of lung cancer.The effect of expression level of TRIM59 in TAMs on the function of lung cancer cells was further verified via in vitro up-regulating or down-regulating the expression level of TRIM59 in macrophages(THP-1 derived macrophages).Results:The mIHC results showed that the expression level of E3 ubiquitin ligase TRIM59 in TAMs was significantly up-regulated compared to the macrophages in adjacent tissues,and the high expression of E3 ubiquitin ligase TRIM59 in TAMs was related to lymph node metastasis,tumor staging,and distant organ metastasis(P<0.05).Survival analysis indicated that the prognosis was poor in patients with increased expression level of E3 ubiquitin ligase TRIM59 in TAMs(P<0.001).Transwell experiment and colony formation assay demonstrated that overexpressed macrophage of TRIM59 promoted tumor cell invasion and proliferation(P<0.01),yet inhibited expression of macrophage TRIM59 could curb the invasion and proliferation of tumor cells(P<0.01).Conclusion:The expression level of E3 ubiquitin ligase TRIM59 is elevated in TAMs in lung cancer,and its expression level is related to clinicopathological parameters.Higher expression level of TRIM59 in TAMs may mark poorer prognosis of patients,and elevated expression level of TRIM59 in TAMs may promote the proliferation and invasion of tumor

关 键 词：三结构域蛋白59 肿瘤相关巨噬细胞 肺癌 肿瘤细胞侵袭和增殖 

分 类 号：R734.2[医药卫生—肿瘤] R365[医药卫生—临床医学]