Wang Di, Lu Ruichun, Yan Fenglian, Lin Yansong, Wang Hao, Xiong Huabao
Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, 272067, China.
Department of Cadre Healthcare/Geriatrics, Qingdao Hospital, University of Health Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266017, China.
J Transl Med. 2025 Feb 21;23(1):213. doi: 10.1186/s12967-025-06252-5.
Gastrointestinal metastases are rare in patients with thyroid carcinoma (TC), and their underlying mechanisms remain unclear. Thus, in this study, we aimed to explore the spatial distribution characteristics of TCs and associated gastrointestinal metastatic cells.
We used spatial transcriptomics to generate an atlas that captures spatial gene expression patterns in papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC), ATC-associated lymphatic metastasis (ATC-LM), and rare ATC-associated gastric metastasis (ATC-GM).
We demonstrated that tumor-specific myeloid cells with high SFRP4 expression were correlated with TC dedifferentiation and poor prognosis. Moreover, we validated their close localization to CD44 tissue stem cells using immunofluorescence staining and spatial transcriptomics. We also demonstrated that ATC-LM and ATC-GM tissues exhibited high levels of CD44PKHD1L1 cells, which could serve as markers for these two pathological types.
These findings highlight the dynamic changes in cell composition, intercellular communication, and potential markers associated with TC dedifferentiation and distant metastasis. Further research based on our findings may contribute to improving diagnostic and therapeutic strategies for patients with TC.
甲状腺癌(TC)患者发生胃肠道转移较为罕见,其潜在机制尚不清楚。因此,在本研究中,我们旨在探索甲状腺癌及相关胃肠道转移细胞的空间分布特征。
我们使用空间转录组学生成了一个图谱,该图谱捕捉了乳头状甲状腺癌(PTC)、间变性甲状腺癌(ATC)、ATC相关淋巴转移(ATC-LM)和罕见的ATC相关胃转移(ATC-GM)中的空间基因表达模式。
我们证明,高表达SFRP4的肿瘤特异性髓样细胞与TC去分化和不良预后相关。此外,我们通过免疫荧光染色和空间转录组学验证了它们与CD44组织干细胞的紧密定位。我们还证明,ATC-LM和ATC-GM组织中CD44PKHD1L1细胞水平较高,可作为这两种病理类型的标志物。
这些发现突出了与TC去分化和远处转移相关的细胞组成、细胞间通讯及潜在标志物的动态变化。基于我们的发现开展进一步研究可能有助于改善TC患者的诊断和治疗策略。