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

• Published in: Nature communications Vol. 12; no. 1; p. 6058
• Main Authors: Pu, Weilin, Shi, Xiao, Yu, Pengcheng, Zhang, Meiying, Liu, Zhiyan, Tan, Licheng, Han, Peizhen, Wang, Yu, Ji, Dongmei, Gan, Hualei, Wei, Wenjun, Lu, Zhongwu, Qu, Ning, Hu, Jiaqian, Hu, Xiaohua, Luo, Zaili, Li, Huajun, Ji, Qinghai, Wang, Jiucun, Zhang, Xiaoming, Wang, Yu-Long
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 18.10.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Angiogenesis; Antiangiogenics; Cancer; Crosstalk; Ecosystems; Fibroblasts; Gene sequencing; Immunotherapy; Iodine; Iodine radioisotopes; Lymph nodes; Mesenchyme; Metastases; Microenvironments; Morphology; Papillary thyroid carcinoma; Patients; Phenotypes; Thyrocytes; Thyroid; Thyroid cancer; Transcriptomes; Tumor microenvironment; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26343-3

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.