Scholarlink

<p>Foveolar-type gastric adenoma with raspberry-like appearance (FGA-RA) is a rare subtype of <i>Helicobacter pylori</i>–naïve gastric neoplasm characterized by its small, reddish, polypoid morphology. This study aimed to clarify the molecular basis of its epithelial phenotype and the superficial capillary proliferation characteristic of FGA-RA’s reddish appearance by examining alterations in mucin gene expression and angiogenesis-related pathways using spatial transcriptomic profiling and immunohistochemistry. Formalin-fixed, paraffin-embedded tissue from a representative case of FGA-RA was analyzed using the Visium spatial transcriptomics platform (10 × Genomics). Spatial gene mapping revealed diffuse MUC5AC expression throughout the tumor epithelium, consistent with a foveolar phenotype. Notably, MUC17—typically restricted to intestinal enterocytes—was aberrantly coexpressed with MUC5AC in the superficial tumor layer, while MUC2 was absent, suggesting skewed differentiation toward absorptive enterocytes without goblet cell lineage. To validate these findings, immunohistochemical staining for MUC5AC and MUC17 was performed on six biopsy specimens from genetically validated FGA-RA cases harboring the characteristic KLF4 mutation, five of which showed overlapping superficial expression of both MUC5AC and MUC17. Spatial transcriptomic analysis also demonstrated elevated VEGFA expression in tumor and inflammatory cells, and FLT1 expression in superficial stromal endothelial cells. This expression pattern correlated with vascular markers and may contribute to the prominent capillary proliferation seen in FGA-RA. FGA-RA exhibits a distinctive mucin profile reflecting incomplete intestinal differentiation due to KLF4 dysfunction. The characteristic raspberry-like morphology may be a consequence of VEGF-driven angiogenesis induced by chronic stimulation of a superficially compromised epithelium, suggesting that this unique appearance arises from sequential epithelial and stromal alterations orchestrated by KLF4 mutation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Spatial transcriptomic analysis of foveolar-type gastric adenoma with raspberry-like appearance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月20日

查看全文
  • Sohei Kitazawa,
  • Eiji Takeshita,
  • Hideomi Tomida,
  • Teruki Miyake,
  • Yoshio Ikeda,
  • Seiya Bekku,
  • Ryuma Haraguchi,
  • Yuki Takaoka,
  • Teruyuki Ohno,
  • Mashio Taniwaki,
  • Yoichi Hiasa,
  • Riko Kitazawa

摘要

Foveolar-type gastric adenoma with raspberry-like appearance (FGA-RA) is a rare subtype of Helicobacter pylori–naïve gastric neoplasm characterized by its small, reddish, polypoid morphology. This study aimed to clarify the molecular basis of its epithelial phenotype and the superficial capillary proliferation characteristic of FGA-RA’s reddish appearance by examining alterations in mucin gene expression and angiogenesis-related pathways using spatial transcriptomic profiling and immunohistochemistry. Formalin-fixed, paraffin-embedded tissue from a representative case of FGA-RA was analyzed using the Visium spatial transcriptomics platform (10 × Genomics). Spatial gene mapping revealed diffuse MUC5AC expression throughout the tumor epithelium, consistent with a foveolar phenotype. Notably, MUC17—typically restricted to intestinal enterocytes—was aberrantly coexpressed with MUC5AC in the superficial tumor layer, while MUC2 was absent, suggesting skewed differentiation toward absorptive enterocytes without goblet cell lineage. To validate these findings, immunohistochemical staining for MUC5AC and MUC17 was performed on six biopsy specimens from genetically validated FGA-RA cases harboring the characteristic KLF4 mutation, five of which showed overlapping superficial expression of both MUC5AC and MUC17. Spatial transcriptomic analysis also demonstrated elevated VEGFA expression in tumor and inflammatory cells, and FLT1 expression in superficial stromal endothelial cells. This expression pattern correlated with vascular markers and may contribute to the prominent capillary proliferation seen in FGA-RA. FGA-RA exhibits a distinctive mucin profile reflecting incomplete intestinal differentiation due to KLF4 dysfunction. The characteristic raspberry-like morphology may be a consequence of VEGF-driven angiogenesis induced by chronic stimulation of a superficially compromised epithelium, suggesting that this unique appearance arises from sequential epithelial and stromal alterations orchestrated by KLF4 mutation.