Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma

Weilin Pu, Xiao Shi, Pengcheng Yu, Meiying Zhang, Zhiyan Liu, Licheng Tan, Peizhen Han, Yu Wang, Dongmei Ji, Hualei Gan, Wenjun Wei, Zhongwu Lu, Ning Qu, Jiaqian Hu, Xiaohua Hu, Zaili Luo, Huajun Li, Qinghai Ji, Jiucun Wang, Xiaoming Zhang () and Yu-Long Wang ()
Additional contact information
Weilin Pu: Fudan University Shanghai Cancer Center
Xiao Shi: Fudan University Shanghai Cancer Center
Pengcheng Yu: Fudan University Shanghai Cancer Center
Meiying Zhang: Chinese Academy of Sciences
Zhiyan Liu: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Licheng Tan: Fudan University Shanghai Cancer Center
Peizhen Han: Fudan University Shanghai Cancer Center
Yu Wang: Fudan University Shanghai Cancer Center
Dongmei Ji: Fudan University
Hualei Gan: Fudan University
Wenjun Wei: Fudan University Shanghai Cancer Center
Zhongwu Lu: Fudan University Shanghai Cancer Center
Ning Qu: Fudan University Shanghai Cancer Center
Jiaqian Hu: Fudan University Shanghai Cancer Center
Xiaohua Hu: Fudan University
Zaili Luo: Cincinnati Children’s Hospital Medical Center
Huajun Li: Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Qinghai Ji: Fudan University Shanghai Cancer Center
Jiucun Wang: Fudan University
Xiaoming Zhang: Chinese Academy of Sciences
Yu-Long Wang: Fudan University Shanghai Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26343-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26343-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26343-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().