Proteomic analysis of radioiodine-refractory differentiated thyroid cancer identifies CHI3L1 upregulation in association with dysfunction of the sodium-iodine symporter

作者全名："Li, Yunjie; Hu, Fengqiong; Deng, Jie; Huang, Xin; Zhou, Chunyan; Wu, Mengxue; Duan, Dong"

作者地址："[Li, Yunjie] Second Peoples Hosp Shenzhen, Dept Nucl Med, Shenzhen 518035, Guangdong, Peoples R China; [Hu, Fengqiong; Huang, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Nucl Med, Chongqing 400016, Peoples R China; [Deng, Jie] Army Med Univ, Affiliated Hosp 2, Dept Nucl Med, Chongqing 400037, Peoples R China; [Zhou, Chunyan; Duan, Dong] Chongqing Gen Hosp, Dept Nucl Med, Chongqing 401147, Peoples R China; [Wu, Mengxue] Army Med Univ, Hosp Affiliated 1, Dept Nucl Med, Chongqing 400038, Peoples R China; [Duan, Dong] Chongqing Gen Hosp, Dept Nucl Med, 118 Xingguang Ave, Chongqing 401147, Peoples R China"

通信作者："Duan, D (通讯作者)，Chongqing Gen Hosp, Dept Nucl Med, 118 Xingguang Ave, Chongqing 401147, Peoples R China."

来源：ONCOLOGY LETTERS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000901367600001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：25

期号：1

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结束页：　

文献类型：Article

关键词：comparative proteomics; radioiodine-refractory thyroid cancer; chitinase-3-like 1; sodium-iodine symporter; targeting therapy

摘要："Radioiodine refractory differentiated thyroid cancer (RR-DTC) is the main factor adversely affecting the overall survival rate of patients with thyroid cancer. The aim of the present study was to investigate the underlying molecular mechanism of pathogenesis of RR-DTC and to explore novel therapeutic targets for clinical treatment. A proteomic analysis was performed using the tumor tissues of patients with RR-DTC. A total of 6 metastatic lymph nodes were collected during lymph node dissection, 3 from patients with RR-DTC and 3 from patients with papillary thyroid cancer. The expression of chitinase-3-like 1 (CHI3L1) and sodium-iodine symporter (NIS) in the tumor tissue was detected by immunohistochemistry (IHC). Western blotting was used to detect the expression of CHI3L1, phosphorylated (p)-MEK and p-ERK1/2 in PTC-K1 cells transfected with CHI3L1 overexpression vector. The proteomic analysis identified 665 differentially expressed proteins (DEPs), including 327 upregulated and 338 downregulated proteins in the RR-DTC group, which were enriched in 59 signaling pathways by Kyoto Encyclopedia of Genes and Genomes database analysis. In particular, CHI3L1 was demonstrated to be significantly upregulated in RR-DTC as evidenced by quantitative proteomic analysis and IHC. Western blotting suggested that the overexpression of CHI3L1 activated the MEK/ERK1/2 signaling pathway, which may lead to NIS dysfunction. In conclusion, the present study suggests that CHI3L1 is a potential molecular target for the radiotherapy of patients with RR-DTC."

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