CST6在甲状腺乳头状癌中的表达及对细胞生物学功能的影响  

Expression of CST6 in thyroid papillary carcinoma and its effect on cell biological function

作　　者：胡锦波 张璐[2] 牛海刚[1,3] 郭文科 田晓爱 郭建平 HU Jinbo;ZHANG Lu;NIU Haigang;GUO Wenke;TIAN Xiaoai;GUO Jianping(Fenyang College of Shanxi Medical University,Shanxi Lvliang 032200,China;Affiliated Hospital of Hebei University,Hebei Baoding 071000,China;Fenyang Hospital,Shanxi Province,Shanxi Lvliang 032200,China)

机构地区：[1]山西医科大学汾阳学院,山西吕梁032200 [2]河北大学附属医院,河北保定071000 [3]山西省汾阳医院,山西吕梁032200

出　　处：《现代肿瘤医学》2024年第22期4235-4244,共10页Journal of Modern Oncology

基　　金：山西省吕梁市重点研发项目(编号:2020SHFZ63);山西省汾阳医院科技攻关项目(编号:202305)。

摘　　要：目的:研究半胱氨酸蛋白酶抑制因子6(Cystatin M/E,Cystatin 6,CST6)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中的表达情况及其与颈部淋巴结转移的相关性,以及CST6表达与PTC细胞恶性生物学行为的关系,并初步探索其作用通路。方法:选取119例PTC患者,应用免疫组化检测PTC及甲状腺滤泡上皮组织中CST6蛋白的表达情况,通过RT-qPCR、Western Blot检测CST6在人甲状腺乳头状癌细胞株TPC-1、K1、B-CPAP以及人甲状腺正常细胞株Nthy-ori 3-1中蛋白表达水平。根据表达情况筛选并构建CST6过表达及干扰细胞株,通过Transwell及Wound-Healing实验测定PTC细胞侵袭、迁移能力变化。Western Blot检测上皮-间充质转化(epithelial-mesenchymal transition,EMT)关键蛋白(E-cadherin、N-cadherin、Vimentin)变化趋势。结果:与正常甲状腺组织相比,CST6在PTC组织中表达水平较低,并且CST6在pN1患者甲状腺滤泡上皮与pN0患者甲状腺癌组织中高表达。CST6表达水平与肿瘤长径(P<0.0001)以及颈部淋巴结转移(P<0.0003)相关。与OE-CST6组相比,sh-CST6组具有更强烈的侵袭、迁移趋势。同时sh-CST6组E-cadherin蛋白表达明显下调,N-cadherin及Vimentin蛋白表达明显上调(P<0.05)。结论:CST6作为保护性因子,在PTC中低表达,其表达程度与淋巴结转移相关。过表达CST6蛋白能抑制PTC细胞迁移、侵袭能力,同时减少经上皮-间质转化途径导致的颈部淋巴结转移。Objective:To study the expression of cysteine protease inhibitory factor 6(Cystatin M/E,Cystatin 6,CST6)in papillary thyroid carcinoma(PTC)and its correlation with cervical lymph node metastasis,and the relationship between the expression of CST6 and the malignant biological behavior of PTC cells,and initially explore its pathway.relationship between CST6 expression and the malignant biological behavior of PTC cells,and preliminarily explore its pathway of action.Methods:119 PTC patients were selected,and immunohistochemistry was applied to detect CST6 protein expression in PTC and thyroid follicular epithelial tissues,and the protein expression level of CST6 was detected by RT-qPCR and Western Blot in human papillary thyroid carcinoma cell lines TPC-1,K1,and B-CPAP,as well as in human thyroid normal cell line Nthy-ori 3-1.CST6 overexpressing and interfering cell lines were screened and constructed according to the expression status,and changes in the invasion and migration ability of PTC cells were determined by Transwell and Wound-Healing assays.The change trend of key proteins(E-cadherin,N-cadherin,Vimentin)in epithelial-mesenchymal transition(EMT)was detected by Western Blot.Results:Compared with normal thyroid tissues,CST6 was expressed at a lower level in PTC tissues,and CST6 was highly expressed in the follicular epithelium of the thyroid gland of patients with pN 1 versus those of thyroid cancer tissues of patients with pN 0.The expression level of CST6 was correlated with the length of the tumor diameter(P<0.0001)as well as with the metastasis of the cervical lymph nodes(P<0.0003).Compared with the OE-CST6 group,the sh-CST6 group had a stronger trend of invasion and migration.Meanwhile,E-cadherin protein expression was significantly down-regulated and N-cadherin and Vimentin protein expression was significantly up-regulated in sh-CST6 group(P<0.05).Conclusion:CST6,as a protective factor,was lowly expressed in PTC,and its expression degree was correlated with lymph node metastasis.Overexpression of CST6 p

关 键 词：半胱氨酸蛋白酶抑制因子6 甲状腺乳头状癌 颈部淋巴结转移 上皮-间充质转化 

分 类 号：R736.1[医药卫生—肿瘤]