Liao Tian, Zeng Yu, Xu Weibo, Shi Xiao, Shen Cenkai, Du Yuxin, Zhang Meng, Zhang Yan, Li Ling, Ding Peipei, Hu Weiguo, Huang Zhiheng, Fung Man Him Matrix, Ji Qinghai, Wang Yu, Li Shengli, Wei Wenjun
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China; State Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
Cell Rep Med. 2025 Apr 15;6(4):102043. doi: 10.1016/j.xcrm.2025.102043. Epub 2025 Mar 28.
Tumor microenvironment (TME) remodeling plays a pivotal role in thyroid cancer progression, yet its spatial dynamics remain unclear. In this study, we integrate spatial transcriptomics and single-cell RNA sequencing to map the TME architecture across para-tumor thyroid (PT) tissue, papillary thyroid cancer (PTC), locally advanced PTC (LPTC), and anaplastic thyroid carcinoma (ATC). Our integrative analysis reveals extensive molecular and cellular heterogeneity during thyroid cancer progression, enabling the identification of three distinct thyrocyte meta-clusters, including TGIYG subpopulation in PT, HLA-DRB1HLA-DRA subpopulation in early cancerous stages, and APOEAPOC1 subpopulation in late-stage progression. We reveal stage-specific tumor leading edge remodeling and establish high-confidence cell-cell interactions, such as COL8A1-ITHB1 in PTC, LAMB2-ITGB4 in LPTC, and SERPINE1-PLAUR in ATC. Notably, both SERPINE1 expression level and SERPINE1 fibroblast abundance correlate with malignant progression and prognosis. These findings provide a spatially resolved framework of TME remodeling, offering insights for thyroid cancer diagnosis and treatment.
肿瘤微环境（TME）重塑在甲状腺癌进展中起关键作用，但其空间动态仍不清楚。在本研究中，我们整合空间转录组学和单细胞RNA测序，以绘制副肿瘤甲状腺（PT）组织、乳头状甲状腺癌（PTC）、局部晚期PTC（LPTC）和间变性甲状腺癌（ATC）的TME结构图谱。我们的综合分析揭示了甲状腺癌进展过程中广泛的分子和细胞异质性，从而能够识别出三个不同的甲状腺细胞元簇，包括PT中的TGIYG亚群、癌前期的HLA-DRB1HLA-DRA亚群以及晚期进展中的APOEAPOC1亚群。我们揭示了阶段特异性的肿瘤前沿重塑，并建立了高可信度的细胞间相互作用，如PTC中的COL8A1-ITHB1、LPTC中的LAMB2-ITGB4以及ATC中的SERPINE1-PLAUR。值得注意的是，SERPINE1表达水平和SERPINE1成纤维细胞丰度均与恶性进展和预后相关。这些发现提供了一个TME重塑的空间解析框架，为甲状腺癌的诊断和治疗提供了见解。
