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多胺代谢通过调节肿瘤相关巨噬细胞的免疫表型促进甲状腺癌进展。

Polyamine Metabolism Promotes the Progression of Thyroid Carcinoma by Regulating the Immune Phenotype of Tumor Associated Macrophages.

作者信息

Ding Haoran, Xue Lingling, Zhu Shaoshi, Wang Ziyu, Gui Huan, Zhang Guang, Tang Ning, Ren Haozhen, Chen Dayu

机构信息

Division of Thyroid Surgery Department of General Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Medical School Nanjing University Nanjing China.

Division of Hepatobiliary and Transplantation Surgery Department of General Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing China.

出版信息

Smart Med. 2025 May 16;4(2):e70009. doi: 10.1002/smmd.70009. eCollection 2025 Jun.

Abstract

Polyamine metabolism is a key regulator of cellular proliferation and immune modulation, and its dysregulation is implicated in multiple carcinoma pathogenesis. Macrophages also greatly influence tumor progression by regulating the immune microenvironment. However, the role of polyamine metabolism in thyroid cancer macrophages remains understudied. This study explores the connection between polyamine metabolism and macrophages in thyroid cancer. Using the THCA dataset gene expression analysis and single-cell data, we identified macrophage subpopulations. We assessed immune scores, matrix scores, immune checkpoint scores, and immune cell types using Bulk-RNA data and the TIDE platform to predict immune checkpoint inhibitor responses. Clinical specimens validated our findings. Our results show a significant association between polyamine metabolism and the clinical and biological characteristics of thyroid cancer, including macrophage trajectory. Notably, macrophage subpopulations affected by polyamine metabolism have strong prognostic value, especially in immunotherapy patients. We found that changes in these subpopulations correlate with thyroid cancer development, and tumor tissue can regulate macrophage polyamine metabolism. This study provides new insights into how polyamine metabolism affects macrophages and the tumor microenvironment, influencing tumor growth and anti-tumor immune responses in thyroid cancer.

摘要

多胺代谢是细胞增殖和免疫调节的关键调节因子,其失调与多种癌症的发病机制有关。巨噬细胞也通过调节免疫微环境对肿瘤进展产生重大影响。然而,多胺代谢在甲状腺癌巨噬细胞中的作用仍未得到充分研究。本研究探讨了甲状腺癌中多胺代谢与巨噬细胞之间的联系。利用甲状腺癌数据集基因表达分析和单细胞数据,我们鉴定了巨噬细胞亚群。我们使用批量RNA数据和TIDE平台评估免疫评分、基质评分、免疫检查点评分和免疫细胞类型,以预测免疫检查点抑制剂的反应。临床标本验证了我们的发现。我们的结果表明,多胺代谢与甲状腺癌的临床和生物学特征之间存在显著关联,包括巨噬细胞轨迹。值得注意的是,受多胺代谢影响的巨噬细胞亚群具有很强的预后价值,尤其是在免疫治疗患者中。我们发现这些亚群的变化与甲状腺癌的发展相关,并且肿瘤组织可以调节巨噬细胞的多胺代谢。本研究为多胺代谢如何影响巨噬细胞和肿瘤微环境,进而影响甲状腺癌的肿瘤生长和抗肿瘤免疫反应提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37ef/12087399/c71ee9c7ff7f/SMMD-4-e70009-g008.jpg

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