Characterizing dedifferentiation of thyroid cancer by integrated analysis

Han Luo; Xuyang Xia; Gyeong Dae Kim; Yang Liu; Zhinan Xue; Lingyun Zhang; Yang Shu; Tian Yang; Yan Chen; Shouyue Zhang; Haining Chen; Weihan Zhang; Ruicen Li; Huairong Tang; Birong Dong; Xianghui Fu; Wei Cheng; Wei Zhang; Li Yang; Yong Peng; Lunzhi Dai; Hongbo Hu; Yong Jiang; Changyang Gong; Yiguo Hu; Jingqiang Zhu; Zhihui Li; Carlos Caulin; Tao Wei; Jihwan Park; Heng Xu

doi:10.1126/sciadv.abf3657

Characterizing dedifferentiation of thyroid cancer by integrated analysis

Han Luo, Xuyang Xia, Gyeong Dae Kim, Yang Liu, Zhinan Xue, Lingyun Zhang, Yang Shu, Tian Yang, Yan Chen, Shouyue Zhang, Haining Chen, Weihan Zhang, Ruicen Li, Huairong Tang, Birong Dong, Xianghui Fu, Wei Cheng, Wei Zhang, Li Yang, Yong PengLunzhi Dai, Hongbo Hu, Yong Jiang, Changyang Gong, Yiguo Hu, Jingqiang Zhu, Zhihui Li, Carlos Caulin, Tao Wei, Jihwan Park, Heng Xu

Otolaryngology

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Article number	eabf3657
Journal	Science Advances
Volume	7
Issue number	31
DOIs	https://doi.org/10.1126/sciadv.abf3657
State	Published - Jul 2021

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Luo, H, Xia, X, Kim, GD, Liu, Y, Xue, Z, Zhang, L, Shu, Y, Yang, T, Chen, Y, Zhang, S, Chen, H, Zhang, W, Li, R, Tang, H, Dong, B, Fu, X, Cheng, W, Zhang, W, Yang, L, Peng, Y, Dai, L, Hu, H, Jiang, Y, Gong, C, Hu, Y, Zhu, J, Li, Z, Caulin, C, Wei, T, Park, J & Xu, H 2021, 'Characterizing dedifferentiation of thyroid cancer by integrated analysis', Science Advances, vol. 7, no. 31, eabf3657. https://doi.org/10.1126/sciadv.abf3657

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title = "Characterizing dedifferentiation of thyroid cancer by integrated analysis",

abstract = "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.",

author = "Han Luo and Xuyang Xia and Kim, {Gyeong Dae} and Yang Liu and Zhinan Xue and Lingyun Zhang and Yang Shu and Tian Yang and Yan Chen and Shouyue Zhang and Haining Chen and Weihan Zhang and Ruicen Li and Huairong Tang and Birong Dong and Xianghui Fu and Wei Cheng and Wei Zhang and Li Yang and Yong Peng and Lunzhi Dai and Hongbo Hu and Yong Jiang and Changyang Gong and Yiguo Hu and Jingqiang Zhu and Zhihui Li and Carlos Caulin and Tao Wei and Jihwan Park and Heng Xu",

note = "Publisher Copyright: Copyright {\textcopyright} 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).",

year = "2021",

month = jul,

doi = "10.1126/sciadv.abf3657",

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AU - Luo, Han

AU - Xia, Xuyang

AU - Kim, Gyeong Dae

AU - Liu, Yang

AU - Xue, Zhinan

AU - Zhang, Lingyun

AU - Shu, Yang

AU - Yang, Tian

AU - Chen, Yan

AU - Zhang, Shouyue

AU - Chen, Haining

AU - Zhang, Weihan

AU - Li, Ruicen

AU - Tang, Huairong

AU - Dong, Birong

AU - Fu, Xianghui

AU - Cheng, Wei

AU - Zhang, Wei

AU - Yang, Li

AU - Peng, Yong

AU - Dai, Lunzhi

AU - Hu, Hongbo

AU - Jiang, Yong

AU - Gong, Changyang

AU - Hu, Yiguo

AU - Zhu, Jingqiang

AU - Li, Zhihui

AU - Caulin, Carlos

AU - Wei, Tao

AU - Park, Jihwan

AU - Xu, Heng

N1 - Publisher Copyright: 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).

PY - 2021/7

Y1 - 2021/7

N2 - 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.

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Characterizing dedifferentiation of thyroid cancer by integrated analysis

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