PDF(Pubmed)
Abstract：
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.
摘要：
滤泡性甲状腺癌（FTC）通过其侵入肿瘤囊和血管的能力来识别，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,FTC的空间转录景观通过侵袭性前沿和组织学惰性中央核心肿瘤区域之间的比较进行了详细说明。Visium空间基因表达平台使我们能够在福尔马林固定的石蜡包埋（FFPE）组织切片中以2D询问和可视化整个转录组。对FTC的四个不同的6×6毫米区域进行了仔细检查，包括包膜和血管侵犯的区域，无入侵的胶囊附近区域，和肿瘤的中央核心区域。成功捕获和测序后，确定了几个具有区域差异的表达簇。最值得注意的是,侵袭性肿瘤细胞簇显著过表达与细胞外基质(ECM)重塑和上皮-间质转化(EMT)相互作用的通路相关的基因.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额外验证,显示了从肿瘤核心到外周的清晰梯度模式。此外，进化树的重建将侵袭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FTC的第一个2D全局转录映射之一。侵袭性FTC克隆以逐步方式发展，并显示出与ECM和EMT相关的基因的显着失调-因此突出了重要的分子串扰以供进一步研究。
