Proteomic analysis reveals modulation of key proteins in follicular thyroid cancer progression.
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Cai Xue, Sun Rui, Yang Liang, Yao Nan, Sun Yaoting, Zhang Guangmei, Ge Weigang, Zhou Yan, Gui Zhiqiang, Wang Yu, Zheng Haitao, Xu Dong, Zhao Yongfu, Nie Xiu, Liu Zhiyan, Zhang Hao, Hu Pingping, Cheng Honghan, Xue Zhangzhi, Wang Jiatong, Yu Jing, Chen Chuang, Luo Dingcun, Zhu Jingqiang, Liu Tong, Zhang Yifeng, Wu Qijun, Guo Qiaonan, Chen Wanyuan, Wang Jianbiao, Wei Wenjun, Lin Xiangfeng, Yao Jincao, Wang Guangzhi, Peng Li, Liu Shuyi, Wang Zhihong, Liu Hanqing, Wang Jiaxi, Wu Fan, Yuan Zhennan, Gong Tingting, Lyu Yangfan, Xiang Jingjing, Zhu Yi, Xie Lei, Ge Minghua, Guan Haixia, Guo Tiannan, We-TEC Investigators
Аннотация
METHODS: Using parallel reaction monitoring-mass spectrometry (PRM-MS) assays, we identified and quantified 94 differentially expressed protein candidates from a retrospective cohort of 1085 FTC and FTA tissue samples from 18 clinical centers. Of these targeted proteins, those with the potential for distinguishing FTC from FTA were prioritized using machine learning. Co-immunoprecipitation (co-IP) and immunofluorescence co-localization assays, as well as gene interference, overexpression, and immunohistochemistry (IHC) experiments, were used to investigate the interactions and cellular functions of selected proteins.
RESULTS: Using machine learning models and feature selection methods, 30 of the 94 candidates were prioritized as key proteins. Co-IP and immunofluorescence co-localization assays using FTC cell lines revealed interactions among insulin-like growth factor 2 receptor (IGF2R), major vault protein (MVP), histone deacetylase 1 (HDAC1), and histone H1.5 (H1-5). Gene interference and overexpression experiments in FTC-133 cells confirmed the promotional role of these proteins in cell proliferation. IHC assays of patient samples further confirmed elevated expression of these four proteins in FTC compared with that in FTA.
CONCLUSIONS: Our findings underscore the utility of advanced proteomic techniques in elucidating the molecular underpinnings of FTC, highlighting the potential significance of IGF2R, MVP, HDAC1, and H1-5 in FTC progression, and providing a foundation for the exploration of targeted therapies.