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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
引用本文:欧慧婷,李剑,廖梦颖,石晓欣,杨红杰,闫德文.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[J].现代肿瘤医学,2022,0(6):995-1000.
作者姓名:欧慧婷  李剑  廖梦颖  石晓欣  杨红杰  闫德文
作者单位: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;3.核医学科,广东 深圳 518000
基金项目: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(integrin β4,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。

关 键 词:甲状腺乳头状癌  整合素β4  钠碘同向转运体  

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
OU Huiting,LI Jian,LIAO Mengying,SHI Xiaoxin,YANG Hongjie,YAN Dewen.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[J].Journal of Modern Oncology,2022,0(6):995-1000.
Authors:OU Huiting  LI Jian  LIAO Mengying  SHI Xiaoxin  YANG Hongjie  YAN Dewen
Affiliation:1.Department of Endocrinology,Shenzhen Second People's Hospital(the First Affiliated Hospital of Shenzhen University),Guangdong Shenzhen 518028,China;2.Department of Pathology;3.Department of Nuclear Medicine,Peking University Shenzhen Hospital,Guangdong Shenzhen 518000,China.
Abstract: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 125I 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.
Keywords:papillary thyroid carcinoma  integrinβ4  sodium iodide symporter  iodine
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