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Proteomic analysis reveals modulation of key proteins in follicular thyroid cancer progression

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机构: [1]College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China [2]Affiliated Hangzhou First People’s Hospital, State Key Laboratory of Medical Proteomics, School of Medicine, Westlake University, Hangzhou, Zhejiang 310024, China [3]Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310030, China [4]Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China [5]Westlake Omics (Hangzhou) Biotechnology Co., Ltd. Hangzhou, Zhejiang 310024, China [6]Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China [7]Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China [8]Department of Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China [9]Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China [10]Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, China [11]Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China [12]Department of Pathology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200235, China [13]Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China [14]Department of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang 310006, China [15]Division of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [16]Department of Oncology Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China [17]Department of Medical Ultrasound, Shanghai Tenth People’s Hospital.Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Shanghai 200072, China [18]Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China [19]Department of Pathology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China [20]Department of Pathology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310006, China [21]Department of Head and Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University, The Affiliated Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China [22]Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China [23]Department of Pathology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang 310006, China [24]Otolaryngology and Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310006, China [25]Department of Endocrinology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China
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关键词: Proteomics Thyroid cancer Parallel reaction monitoring mass spectrometry Machine learning Insulin-like growth factor 2 receptor Major vault protein Histone deacetylase 1 Histone H1 5

摘要:
Cytopathology cannot be used to reliably distinguish follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), the second most common form of thyroid cancer, because they exhibit nearly identical cellular morphology. Given the challenges in diagnosis and treatment, this study aims to identify the mechanisms underlying FTC is essential.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.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 protei (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.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.Copyright © 2025 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

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大类 | 2 区 医学
小类 | 2 区 医学:内科
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 医学:内科
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第一作者机构: [1]College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China [2]Affiliated Hangzhou First People’s Hospital, State Key Laboratory of Medical Proteomics, School of Medicine, Westlake University, Hangzhou, Zhejiang 310024, China [3]Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310030, China [4]Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China
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通讯机构: [1]College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China [2]Affiliated Hangzhou First People’s Hospital, State Key Laboratory of Medical Proteomics, School of Medicine, Westlake University, Hangzhou, Zhejiang 310024, China [3]Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310030, China [4]Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China
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