Open AccessCharacterizing dedifferentiation of thyroid cancer by integrated analysis
Author(s) -
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 Caulín,
Tao Wei,
Jihwan Park,
Huan Xu
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abf3657
Subject(s) - thyroid cancer , cancer , computational biology , thyroid , computer science , cancer research , biology , medicine
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.