Characterizing dedifferentiation of thyroid cancer by integrated analysis

被引：120

作者：

Luo, Han ^{[1
]}

Xia, Xuyang ^{[2
,3
,4
]}

Kim, Gyeong Dae ^{[5
]}

Liu, Yang ^{[1
]}

Xue, Zhinan ^{[2
,3
,4
]}

Zhang, Lingyun ^{[1
]}

Shu, Yang ^{[2
,3
,4
,6
]}

Yang, Tian ^{[7
]}

Chen, Yan ^{[2
,3
,4
]}

Zhang, Shouyue ^{[2
,3
,4
]}

Chen, Haining ^{[6
]}

Zhang, Weihan ^{[6
]}

Li, Ruicen ^{[8
]}

Tang, Huairong ^{[8
]}

Dong, Birong ^{[9
]}

Fu, Xianghui ^{[2
,3
,4
]}

Cheng, Wei ^{[2
,3
,4
]}

Zhang, Wei ^{[10
]}

Yang, Li ^{[2
,3
,4
]}

Peng, Yong ^{[2
,3
,4
]}

Dai, Lunzhi ^{[2
,3
,4
]}

Hu, Hongbo ^{[2
,3
,4
]}

Jiang, Yong ^{[7
]}

Gong, Changyang ^{[2
,3
,4
]}

Hu, Yiguo ^{[1
,2
,3
,4
]}

Zhu, Jingqiang ^{[1
]}

Li, Zhihui ^{[1
]}

Caulin, Carlos ^{[11
,12
]}

Wei, Tao ^{[1
]}

Park, Jihwan ^{[5
]}

Xu, Heng ^{[2
,3
,4
,13
]}

机构：

[1] Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, Dept Thyroid & Parathyroid Surg,Lab Thyroid & Thy, Chengdu, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

[3] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Sichuan, Peoples R China

[4] Collaborat Innovat Ctr, Chengdu, Sichuan, Peoples R China

[5] Gwangju Inst Sci & Technol GIST, Sch Life Sci, Gwangju, South Korea

[6] Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

[7] Sichuan Univ, West China Hosp, Dept Pathol, Chengdu, Sichuan, Peoples R China

[8] Sichuan Univ, West China Hosp, Hlth Promot Ctr, Chengdu, Sichuan, Peoples R China

[9] Natl Clin Res Ctr Geriatr, Chengdu, Sichuan, Peoples R China

[10] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha, Hunan, Peoples R China

[11] Univ Arizona, Dept Otolaryngol Head & Neck Surg, Tucson, AZ USA

[12] Univ Arizona, Canc Ctr, Tucson, AZ USA

[13] Sichuan Univ, West China Hosp, Dept Lab Med, Precis Med Ctr,State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 31期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

EXPRESSION; CARCINOMA; PAPILLARY; PROGRESSION; BRAF; DIFFERENTIATION; BRAF(V600E); ACTIVATION; REVEALS; GENES;

D O I：

10.1126/sciadv.abf3657

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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