RIP1、MLKL蛋白在未分化甲状腺癌中的表达及临床意义  

Expression and clinical significance of receptor interacting protein kinase 1(RIP1)and mixed-lineage kinase domain-like protein(MLKL)proteins in anaplastic thyroid carcinoma(ATC)

作　　者：姜燕 郭越 王芳 张学 牛彦斌 JIANG Yan;GUO Yue;WANG Fang;ZHANG Xue;NIU Yanbin(Central Operating Room,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China)

机构地区：[1]山西白求恩医院/山西医学科学院/同济山西医院/山西医科大学第三医院中心手术部,太原030032

出　　处：《新疆医科大学学报》2024年第2期238-243,共6页Journal of Xinjiang Medical University

基　　金：山西省应用基础研究计划项目(201901D211533)。

摘　　要：目的探讨受体相互作用蛋白激酶1(RIP1)、混合系激酶区域样蛋白(MLKL)在未分化甲状腺癌(ATC)中的表达及其临床意义。方法选取48例ATC患者为研究对象,检测手术标本组织中RIP1、MLKL的表达,收集患者临床病理参数并随访,统计分析RIP1、MLKL在ATC组织标本中的表达模式及对患者预后的影响。培养人未分化型甲状腺癌THJ-11T、THJ-16T、THJ-21T、ASH-3、BHT101细胞系、分化型甲状腺癌细胞系CAL-62、PDTC-1、正常人甲状腺细胞系Nthy-ori 3-1、HTORI-3,利用Western blot法及RT-PCR检测细胞系中RIP1、MLKL的蛋白mRNA的表达水平。结果(1)RT-PCR及Western blot检测显示,与正常人甲状腺细胞系及分化型甲状腺癌细胞系相比,未分化甲状腺癌细胞系中RIP1、MLKL蛋白和mRNA相对表达水平明显更高。(2)48例ATC患者中,14例起源于乳头状甲状腺癌(PTC),34例起源于滤泡状甲状腺癌(FTC)。肿瘤细胞表现出明显的多形性。形态学特征包括梭形细胞为主的肉瘤样及鳞状细胞样。(3)免疫组化染色显示,RIP1表达主要定位于ATC细胞膜。48例ATCs中有24例(50.0%)RIP1染色阳性。组织中含有混合岛状或低分化癌成分。MLKL阳性细胞核表达清晰,48例ATC患者中有29例(60.4%)患者MLKL染色阳性。(4)Kaplan-Meier生存分析显示,RIP1和MLKL过度表达会缩短ATC患者的无病生存期(DFS)(P<0.05),但对患者的总体生存率(OS)无明显影响(P>0.05)。Cox多因素分析显示,RIP1高表达、MLKL高表达、N分期、M分期均是影响ATC患者DFS的独立性危险因素(P<0.05)。结论RIP1、MLKL高表达与ATC的发生及DFS密切相关,或可作为ATC潜在的治疗靶点及预后预测的生物学标记物。Objective To investigate the expression and clinical significance of receptor interacting protein kinase 1(RIP1)and mixed-lineage kinase domain-like protein(MLKL)in anaplastic thyroid carcinoma(ATC).Methods 48 patients with ATC were selected as research object.The expressions of RIP1 and MLKL in surgical specimens were detected.The expression patterns of RIP1 and MLKL in ATC tissues and their effects on the prognosis of the patients were statistically analyzed.THJ-11T,THJ-16T,THJ-21T,ASH-3,BHT101,CAL-62,PDTC-1,Nthyori 3-1 and HTORI-3 were cultured to detect the protein mRNA expression of RIP1 and MLKL in the cell line.Results(1)Compared with normal human thyroid cell lines and differentiated thyroid cancer cell lines,the relative expression levels of RIP1 and MLKL protein and mRNA in undifferentiated thyroid cancer cell lines were significantly higher.(2)Of the 48 patients with ATC,14 originated from papillary thyroid carcinoma(PTC)and 34 from follicular thyroid carcinoma(FTC).The tumor cells showed obvious polymorphism.Morphological features included sarcomatoid and squamous cells with spindle cells predominant.(3)RIP1 expression was mainly localized in ATC cell membrane.RIP1 staining was positive in 24(50.0%)of 48 ATC patients.The tissue contains mixed island or poorly differentiated cancer components.The expression of MLKL positive nuclei was clear.29(60.4%)of 48 ATCs were positive for MLKL.(4)Kaplan-Meier survival analysis showed that overexpression of RIP1 and MLKL can shorten disease-free survival(DFS)in ATC patients(P<0.05),but it had no significant effect on overall survival rate(OS)in ATC patients(P>0.05).High expression of RIP1,high expression of MLKL,N stage and M stage were independent risk factors for DFS in patients with ATC(P<0.05).Conclusion The high expression of RIP1 and MLKL are closely related to the occurrence and DFS of ATC,which can be used as potential therapeutic targets and biological markers for prognosis prediction of ATC.

关 键 词：甲状腺未分化癌 受体相互作用蛋白激酶1(RIP1) 混合系激酶区域样蛋白(MLKL) 

分 类 号：R736.1[医药卫生—肿瘤]