基于iTRAQ技术的碘难治型甲状腺癌与分化型甲状腺癌的比较蛋白质组学研究  

Comparative proteomic analysis of differentiated thyroid carcinoma and radioiodine-refractory differentiated thyroid carcinoma based on iTRAQ technique

作　　者：李运洁 黄鑫[1] 邓婕 段东[1] LI Yunjie;HUANG Xin;DENG Jie;DUAN Dong(Department of Nuclear Medicine,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China)

机构地区：[1]重庆医科大学附属第一医院核医学科

出　　处：《第三军医大学学报》2019年第24期2425-2429,共5页Journal of Third Military Medical University

基　　金：重庆市自然科学基金面上项目(CSTC2019jcyj-msxmX0327)~~

摘　　要：目的寻找碘难治型甲状腺癌和分化型甲状腺癌之间的差异蛋白,探讨碘难治型甲状腺癌发生的机制,探索可能的核素分子治疗靶点。方法收集2018年6月至2019年3月本科收治的碘难治型甲状腺癌和分化型甲状腺癌患者颈部转移淋巴结各3例,利用iTRAQ技术联合质谱分析得到差异蛋白,并通过生物信息学方法对差异蛋白进行GO功能注释、KEGG通路分析,并利用TCGA、TCPA数据库对部分差异蛋白进行验证。结果鉴定得到的差异蛋白共665个,其中显著上调的蛋白327个,显著下调的蛋白338个。ECM1、CHI3L1、LAMA5、14-3-3 eta、CDC42、RAC2、MYL9等差异蛋白广泛参与肿瘤血管生成、侵袭转移及细胞失分化过程。同时,差异蛋白富集于包括代谢通路、黏着斑及其他多条信号通路。结论碘难治型甲状腺癌和分化型甲状腺癌的差异蛋白较多,其主要功能涉及调节转运体活性及酶活性等,参与细胞代谢等多个生物过程。ECM1、CHI3L1及CDC42通过与MAPK通路中部分蛋白相互作用促进肿瘤发展,可能成为核素治疗的潜在靶点。Objective To identify the differentially expressed proteins between differentiated thyroid carcinoma and radioiodine-refractory differentiated thyroid carcinoma,explore the pathogenetic mechanism of radioiodine-refractory differentiated thyroid carcinoma,and identify potential targets for nuclide molecular therapy.Methods We collected the samples of metastatic lymph nodes from 3 patients with radioiodine-refractory differentiated thyroid carcinoma and 3 patients with differentiated thyroid carcinoma treated in our department between June,2018 and March,2019.The differential proteins were detected using iTRAQ technique coupled with mass spectrometry.The raw data of iTRAQ were analyzed with a bioinformatic approach for annotating the function of the differential proteins using GO database and analyzing the interaction of the proteins in KEGG signaling pathways.Some of the differential proteins were verified by analysis of TCGA and TCPA databases.Results We identified a total of 665 differential proteins between the 2 cancers,including 327 significantly up-regulated proteins and 338 down-regulated proteins.The differential proteins,including ECM1,CHI3 L1,LAMA5,14-3-3 eta,CDC42,RAC2,and MYL9,participated in the regulation of tumor angiogenesis,invasion,metastasis,and cell dedifferentiation.The differential proteins were significantly enriched in multiple signaling pathways involved in cell metabolism,focal adhesion,and other cell processes.Conclusion Many proteins are differentially expressed between differentiated thyroid carcinoma and radioiodine-refractory differentiated thyroid carcinoma.These proteins are involved in the regulation of the activity of transporters and enzymes and participate in multiple biological processes.Among these differential proteins,ECM1,CHI3 L1,and CDC42 promote tumor progression by interacting with the proteins in the MAPK signaling pathway,and may serve as potential targets for radionuclide therapy.

关 键 词：碘难治型甲状腺癌 蛋白质组学 同位素标记相对和绝对定量技术 

分 类 号：R341[医药卫生—基础医学] R394.3