Comprehensive single-cell RNA analysis reveals intertumoral microenvironment heterogeneity and hub niche of carcinogenesis in thyroid cancer

作者：Hao Xu, Junjie Ma, Nanjun Li, Haoxiang Xuan, Shijie Lin, Yunuo Shen, Lu Yin, Ping Wang, Qianhui Xu · 发表于：npj Precision Oncology · 年份：2025 · DOI：10.1038/s41698-025-00924-7 · 被引用次数：4 · 研究领域：Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis、Thyroid Cancer Diagnosis and Treatment

Thyroid cancer, the most common endocrine malignancy, is characterized by a unique and complex tumor microenvironment (TME). To unravel the high tumor heterogeneity and molecular mechanisms driving cancer progression, we performed single-cell RNA sequencing (scRNA-seq) analysis, enabling a comprehensive exploration of cellular diversity and molecular dynamics at single-cell resolution. We employed Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and subsequent identification of cellular clusters. Differential gene expression analysis across subclusters was conducted using the FindAllMarkers function, while the DoHeatmap function was utilized to visualize the distribution of differentially expressed genes. The AUCell algorithm was applied to evaluate pathway enrichment within specific cell subtypes. To decipher cellular communication networks, we integrated the CellChat and NicheNet algorithms, which revealed intricate intercellular signaling interactions. Finally, multiplex immunohistochemistry (mIHC) was performed to validate key cellular interactions identified in silico. By analyzing 405,077 single cells from 50 thyroid cancer samples (including papillary, anaplastic, and metastatic tumors) and 14 normal thyroid tissues, we identified four major cellular subpopulations through unbiased clustering based on gene expression patterns and representative cellular markers. The TME was found to encompass diver...