Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma.
Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma.
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甲状腺乳头状癌发生和进展的肿瘤生态系统的单细胞转录组分析
DOI：
10.1038/s41467-021-26343-3
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发表时间：
2021-10-18
影响因子：
16.6
通讯作者：
Wang YL
中科院分区：
文献类型：
--
作者：
Pu W;Shi X;Yu P;Zhang M;Liu Z;Tan L;Han P;Wang Y;Ji D;Gan H;Wei W;Lu Z;Qu N;Hu J;Hu X;Luo Z;Li H;Ji Q;Wang J;Zhang X;Wang YL
甲状腺乳头状癌（PTC）的肿瘤生态系统的特点不佳。使用单细胞RNA测序，我们分析了来自11名患者的癌旁、局部/晚期肿瘤、初始治疗/复发淋巴结和放射性碘（RAI）难治性远处转移的158，577个细胞的转录组，涵盖了PTC的全面临床过程。我们的数据确定了一个“癌致敏”癌前甲状腺细胞的人口与正常形态，但改变转录组。沿着发展轨迹，我们还发现了恶性甲状腺细胞的三种表型（滤泡样，部分上皮间充质转化样，去分化样），其组成形状散装分子亚型，肿瘤特征和RAI反应。此外，我们发现了一个独特的BRAF样B亚型，主要是去分化样甲状腺细胞，富集癌相关成纤维细胞，预后较差，免疫治疗的前景。此外，PTC中潜在的血管免疫串扰为联合抗血管生成和免疫治疗提供了理论基础。总之，我们的研究结果提供了对PTC生态系统的深入了解，这表明了潜在的预后和治疗意义。甲状腺乳头状癌（PTC）肿瘤微环境的特征仍然至关重要。在这里，作者对11名患者进行了单细胞RNA测序，并确定了在PTC中使用免疫治疗及其与抗血管生成治疗相结合的潜在机会。
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. The characterisation of the papillary thyroid carcinoma (PTC) tumour microenvironment remains crucial. Here, the authors perform single-cell RNA sequencing in 11 patients and identify potential opportunities for the use of immunotherapy and its combination with anti-angiogenic therapy in PTC.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
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影响因子：
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Bakir B;Chiarella AM;Pitarresi JR;Rustgi AK
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作者：
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通讯作者：
Cancer Genome Atlas Research Network
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影响因子：
16.6
作者：
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通讯作者：
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影响因子：
16.6
作者：
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通讯作者：
Butte AJ