Analysis of thyroid carcinoma composition and spatial architecture in the progression of dedifferentiation, lymphatic metastasis, and gastric metastasis.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 CD44(+)PKHD1L1(+) cells, which could serve as markers for these two pathological types. CONCLUSIONS: 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.