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Characterizing dedifferentiation of thyroid cancer by integrated analysis.

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机构: [1]Department of Thyroid and Parathyroid Surgery, Laboratory of Thyroid and ParathyroidDisease, Frontiers Science Center for Disease-related Molecular Network,West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]State KeyLaboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan Universityand Collaborative Innovation Center, Chengdu, Sichuan, China [3]School of Life Sciences,Gwangju Institute of Science and Technology (GIST), Gwangju, Republic ofKorea [4]Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, Sichuan, China [5]Department ofPathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China [6]HealthPromotion Center, West China Hospital, Sichuan University, Chengdu, Sichuan,China [7]National Clinical Research Center for Geriatrics, Chengdu, Sichuan, China [8]Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics,Xiangya Hospital, Central South University, Changsha, Hunan, China [9]Departmentof Otolaryngology—Head & Neck Surgery and University of Arizona Cancer Center,University of Arizona, Tucson, AZ, USA [10]Department of Laboratory Medicine,Precision Medicine Center, State Key Laboratory of Biotherapy, West China Hospital,Sichuan University, Chengdu, Sichuan, China
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Understanding of dedifferentiation, an indicator of poo prognosis for patients with thyroid cancer, has been hampered by imprecise and incomplete characterization of its heterogeneity and its attributes. Using single-cell RNA sequencing, we explored the landscape of thyroid cancer at single-cell resolution with 46,205 cells and delineated its dedifferentiation process and suppressive immune microenvironment. The developmental trajectory indicated that anaplastic thyroid cancer (ATC) cells were derived from a small subset of papillary thyroid cancer (PTC) cells. Moreover, a potential functional role of CREB3L1 on ATC development was revealed by integrated analyses of copy number alteration and transcriptional regulatory network. Multiple genes in differentiation-related pathways (e.g., EMT) were involved as the downstream targets of CREB3L1, increased expression of which can thus predict higher relapse risk of PTC. Collectively, our study provided insights into the heterogeneity and molecular evolution of thyroid cancer and highlighted the potential driver role of CREB3L1 in its dedifferentiation process.Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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出版当年[2021]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
第一作者:
第一作者机构: [1]Department of Thyroid and Parathyroid Surgery, Laboratory of Thyroid and ParathyroidDisease, Frontiers Science Center for Disease-related Molecular Network,West China Hospital, Sichuan University, Chengdu, Sichuan, China
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通讯机构: [2]State KeyLaboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan Universityand Collaborative Innovation Center, Chengdu, Sichuan, China [10]Department of Laboratory Medicine,Precision Medicine Center, State Key Laboratory of Biotherapy, West China Hospital,Sichuan University, Chengdu, Sichuan, China
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