Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution.

Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution.
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单细胞分辨率的甲状腺乳头状癌景观及其与桥本甲状腺炎的免疫学联系。

DOI:
10.3389/fcell.2021.758339
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发表时间:
2021
影响因子:
5.5
通讯作者:
Wu Y
Wu Y
中科院分区:
生物学2区
文献类型:
--
作者:
Pan J;Ye F;Yu C;Zhu Q;Li J;Zhang Y;Tian H;Yao Y;Zhu M;Shen Y;Zhu F;Wang Y;Zhou X;Guo G;Wu Y

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甲状腺乳头状癌(PTC)的肿瘤微环境异质性特征不明显。PTC与桥本甲状腺炎(HT)的关系也存在疑问。在这里,我们使用单细胞RNA测序来绘制8名PTC患者的PTC转录组图谱,其中3名患者同时患有HT。上皮细胞和间充质细胞中预测的拷贝数变异揭示了癌细胞的不同分子特征。基于BRAF V600E突变或淋巴结转移,癌细胞表现出肿瘤间异质性,并且在癌症基因组图谱数据集中鉴定出一些改变的基因与无病生存相关。此外,滤泡上皮细胞的转录因子调节子揭示了PTC伴或不伴HT患者的不同转录激活状态。肿瘤中的免疫细胞表现出不同的转录状态,肿瘤浸润B淋巴细胞的存在主要与并发HT起源有关。B细胞和浆细胞的轨迹分析表明它们具有从HT邻近组织向肿瘤组织迁移的潜力。此外,我们揭示了非免疫细胞,浸润性骨髓细胞和淋巴细胞之间的不同配体受体对。我们的研究结果提供了人类PTC的单细胞景观。这些数据将加深对PTC以及PTC和HT之间免疫学联系的了解。
The tumor microenvironment heterogeneity of papillary thyroid cancer (PTC) is poorly characterized. The relationship between PTC and Hashimoto thyroiditis (HT) is also in doubt. Here, we used single-cell RNA sequencing to map the transcriptome landscape of PTC from eight PTC patients, of which three were concurrent with HT. Predicted copy number variation in epithelial cells and mesenchymal cells revealed the distinct molecular signatures of carcinoma cells. Carcinoma cells demonstrated intertumoral heterogeneity based on BRAF V600E mutation or lymph node metastasis, and some altered genes were identified to be correlated with disease-free survival in The Cancer Genome Atlas datasets. In addition, transcription factor regulons of follicular epithelial cells unveil the different transcription activation state in PTC patients with or without concurrent HT. The immune cells in tumors exhibited distinct transcriptional states, and the presence of tumor-infiltrating B lymphocytes was predominantly linked to concurrent HT origin. Trajectory analysis of B cells and plasma cells suggested their migration potential from HT adjacent tissues to tumor tissues. Furthermore, we revealed diverse ligand–receptor pairs between non-immune cells, infiltrating myeloid cells, and lymphocytes. Our results provided a single-cell landscape of human PTC. These data would deepen the understanding of PTC, as well as the immunological link between PTC and HT.
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