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

Li,Yunjie; Hu,Fengqiong; Deng,Jie; Huang,Xin; Zhou,Chunyan; Wu,Mengxue; Duan,Dong

doi:10.3892/ol.2022.13622

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

Authors:
- Yunjie Li
- Fengqiong Hu
- Jie Deng
- Xin Huang
- Chunyan Zhou
- Mengxue Wu
- Dong Duan
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Affiliations: Department of Nuclear Medicine, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518035, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Nuclear Medicine, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, P.R. China, Department of Nuclear Medicine, Chongqing General Hospital, Chongqing 401147, P.R. China, Department of Nuclear Medicine, The First Hospital Affiliated to Army Medical University, Chongqing 400038, P.R. China
Published online on: December 7, 2022 https://doi.org/10.3892/ol.2022.13622
Article Number: 36
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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