Follicular thyroid carcinoma (FTC) is recognized by its ability to invade the tumor capsule and blood vessels, although the exact molecular signals orchestrating this phenotype remain elusive. In this study, the spatial transcriptional landscape of an FTC is detailed with comparisons between the invasive front and histologically indolent central core tumor areas. The Visium spatial gene expression platform allowed us to interrogate and visualize the whole transcriptome in 2D across formalin-fixated paraffin-embedded (FFPE) tissue sections. Four different 6 × 6 mm areas of an FTC were scrutinized, including regions with capsular and vascular invasion, capsule-near area without invasion, and a central core area of the tumor. Following successful capturing and sequencing, several expressional clusters were identified with regional variation. Most notably, invasive tumor cell clusters were significantly over-expressing genes associated with pathways interacting with the extracellular matrix (ECM) remodeling and epithelial-to-mesenchymal transition (EMT). Subsets of these genes (POSTN and DPYSL3) were additionally validated using immunohistochemistry in an independent cohort of follicular thyroid tumors showing a clear gradient pattern from the core to the periphery of the tumor. Moreover, the reconstruction of the evolutionary tree identified the invasive clones as late events in follicular thyroid tumorigenesis. To our knowledge, this is one of the first 2D global transcriptional mappings of FTC using this platform to date. Invasive FTC clones develop in a stepwise fashion and display significant dysregulation of genes associated with the ECM and EMT — thus highlighting important molecular crosstalk for further investigations.

滤泡性甲状腺癌（FTC）因其侵入肿瘤包膜和血管的能力而被识别，尽管协调这种表型的确切分子信号仍然难以捉摸。在这项研究中，通过比较侵袭性前沿和组织学上惰性的中央核心肿瘤区域，详细描述了 FTC 的空间转录景观。Visium 空间基因表达平台使我们能够在福尔马林固定石蜡包埋 (FFPE) 组织切片中以二维方式询问和可视化整个转录组。检查 FTC 的四个不同的 6 × 6 mm 区域，包括有包膜和血管侵犯的区域、无侵犯的近包膜区域以及肿瘤的中央核心区域。成功捕获和测序后，鉴定出几个具有区域变异的表达簇。最值得注意的是，侵袭性肿瘤细胞簇显着过度表达与细胞外基质（ECM）重塑和上皮间质转化（EMT）相互作用的途径相关的基因。这些基因的子集（POSTN和DPYSL3）在独立的滤泡性甲状腺肿瘤队列中使用免疫组织化学进行了验证，显示从肿瘤核心到外围的清晰梯度模式。此外，进化树的重建将侵入性克隆鉴定为滤泡性甲状腺肿瘤发生的晚期事件。据我们所知，这是迄今为止使用该平台的第一个 FTC 2D 全球转录图谱之一。侵入性 FTC 克隆以逐步的方式发育，并表现出与 ECM 和 EMT 相关的基因的显着失调，从而突出了重要的分子串扰以供进一步研究。