高临床分期甲状腺乳头状癌组织中ITGB4与NIS表达的相关性及其对肿瘤细胞摄碘功能的影响  

The correlation between ITGB4 and NIS expression in advanced stage papillary thyroid carcinoma and the effect of ITGB4 on the iodine uptake of thyroid carcinoma cell

作　　者：欧慧婷[1] 李剑[2] 廖梦颖 石晓欣 杨红杰[3] 闫德文 OU Huiting;LI Jian;LIAO Mengying;SHI Xiaoxin;YANG Hongjie;YAN Dewen(Department of Endocrinology,Shenzhen Second People's Hospital(the First Affiliated Hospital of Shenzhen University),Guangdong Shenzhen 518028,China;Department of Pathology,Peking University Shenzhen Hospital,Guangdong Shenzhen 518000,China;Department of Nuclear Medicine,Peking University Shenzhen Hospital,Guangdong Shenzhen 518000,China)

机构地区：[1]深圳市第二人民医院(深圳大学第一附属医院)内分泌科,广东深圳518028 [2]北京大学深圳医院病理科,广东深圳518000 [3]北京大学深圳医院核医学科,广东深圳518000

出　　处：《现代肿瘤医学》2022年第6期995-1000,共6页Journal of Modern Oncology

基　　金：深圳市卫计委立项项目(编号:SZFZ2018074)。

摘　　要：目的:探讨高临床分期甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中整合素β4(integrinβ4,ITGB4)与钠碘同向转运体(sodium iodide symporter,NIS)表达的相关性,评价ITGB4对乳头状癌细胞NIS表达及摄碘功能的影响。方法:收集55例高临床分期PTC切除标本(Ⅲ期45例,Ⅳ期10例),通过免疫组化与RT-qPCR方法,分析组织中ITGB4与NIS表达的相关性。利用慢病毒RNA干扰方法敲减乳头状癌K1细胞中ITGB4水平,检测细胞NIS膜蛋白表达水平的变化,并通过细胞摄碘率实验,观察细胞摄碘率的变化。结果:55例高临床分期PTC标本组织中,ITGB4蛋白高表达组NIS阳性表达率为0%,ITGB4蛋白低表达组NIS阳性表达率为26.67%,两组间有显著差异(P=0.006)。Pearson相关分析显示,ITGB4与NIS mRNA表达水平呈负相关(r=-0.31,P=0.03)。ITGB4敲减组(shRNA-β4)与阴性对照组(shRNA-scr)比较,敲减组K1细胞NIS膜蛋白的表达水平显著升高(P=0.003);自10 min观察点起至70 min观察点止,敲减组K1细胞的摄碘率均显著高于阴性对照组。结论:ITGB4对NIS具有潜在的负向调控作用。阻遏ITBG4水平能促进NIS表达,提升PTC摄碘效能,有望成为碘难治性甲状腺癌新的治疗靶点。Objective:To investigate the correlation between integrinβ4(ITGB4)and sodium iodide symporter(NIS)expression in advanced stage papillary thyroid carcinoma(PTC)and evaluate the effect of ITGB4 on NIS expression and iodine uptake of thyroid carcinoma cell.Methods:55 cases of advanced stage PTC,including 45 cases of stageⅢand 10 cases of stageⅣ,were enrolled.The correlation between expression of ITGB4 and NIS was analyzed by immunohistochemistry and RT-qPCR.Lentiviral RNA interference(RNAi)was employed to knock down the level of ITGB4 in K1 cell and then the changes of NIS membrane protein expression and ^(125)I uptake rate were evaluated by Western blot and gamma counter,respectively.Results:The positive rates of NIS protein in ITGB4 high and low expression group were 0%and 26.67%,respectively,which displayed a significant difference between the two groups(P=0.006).In addition,there was a negative correlation between ITGB4 and NIS mRNA expression(r=-0.31,P=0.03)among the enrolled PTC cases.NIS membrane protein expression in ITGB4 knockdown-treated group(shRNA-β4)was significantly increased in comparison with the control group(shRNA-scr)(P=0.003).Furthermore,the iodine uptake rates of the shRNA-β4 group were significantly higher than that of shRNA-scr group at all the nine observation points in the period of 10 min to 70 min.Conclusion:Suppression of ITGB4 level in PTC could promote the NIS expression and improve the iodine uptake efficiency.ITGB4 is expected to become a potential therapeutic target for iodine refractory PTC.

关 键 词：甲状腺乳头状癌 整合素β4 钠碘同向转运体 碘 

分 类 号：R736.1[医药卫生—肿瘤]