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桥本甲状腺炎对甲状腺乳头状癌肿瘤微环境的影响：单细胞分析的见解。

Impact of Hashimoto's thyroiditis on the tumor microenvironment in papillary thyroid cancer: insights from single-cell analysis.

机构信息

Department of Pharmacogenomics, College of Bioinformatics and Science Technology, Harbin Medical University, Harbin, China.

Department of Urology Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Endocrinol (Lausanne). 2024 Sep 16;15:1339473. doi: 10.3389/fendo.2024.1339473. eCollection 2024.

DOI:10.3389/fendo.2024.1339473
PMID:39351536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11439672/
Abstract

This study investigates the impact of Hashimoto's thyroiditis (HT), an autoimmune disorder, on the papillary thyroid cancer (PTC) microenvironment using a dataset of 140,456 cells from 11 patients. By comparing PTC cases with and without HT, we identify HT-specific cell populations (HASCs) and their role in creating a TSH-suppressive environment via mTE3, nTE0, and nTE2 thyroid cells. These cells facilitate intricate immune-stromal communication through the MIF-(CD74+CXCR4) axis, emphasizing immune regulation in the TSH context. In the realm of personalized medicine, our HASC-focused analysis within the TCGA-THCA dataset validates the utility of HASC profiling for guiding tailored therapies. Moreover, we introduce a novel, objective method to determine K-means clustering coefficients in copy number variation inference from bulk RNA-seq data, mitigating the arbitrariness in conventional coefficient selection. Collectively, our research presents a detailed single-cell atlas illustrating HT-PTC interactions, deepening our understanding of HT's modulatory effects on PTC microenvironments. It contributes to our understanding of autoimmunity-carcinogenesis dynamics and charts a course for discovering new therapeutic targets in PTC, advancing cancer genomics and immunotherapy research.

摘要

本研究使用来自 11 名患者的 140456 个细胞数据集，调查了自身免疫性疾病桥本甲状腺炎 (HT) 对甲状腺乳头状癌 (PTC) 微环境的影响。通过比较有 HT 和无 HT 的 PTC 病例，我们确定了 HT 特异性细胞群 (HASC) 及其通过 mTE3、nTE0 和 nTE2 甲状腺细胞产生 TSH 抑制环境的作用。这些细胞通过 MIF-(CD74+CXCR4) 轴促进复杂的免疫基质通讯，强调 TSH 背景下的免疫调节。在个性化医学领域，我们在 TCGA-THCA 数据集内以 HASC 为重点的分析验证了 HASC 分析在指导靶向治疗中的效用。此外，我们引入了一种新的、客观的方法，从批量 RNA-seq 数据中推断拷贝数变异的 K-均值聚类系数，减轻了传统系数选择的任意性。总的来说，我们的研究提供了一个详细的单细胞图谱，说明了 HT-PTC 相互作用，加深了我们对 HT 对 PTC 微环境调节作用的理解。它有助于我们理解自身免疫-致癌动力学，并为发现 PTC 中的新治疗靶点指明了方向，推进了癌症基因组学和免疫治疗研究。

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