Comprehensive Molecular Characterizations of Gastric Tissue and Gastric Cancer Revealed by Single-cell RNA-seq

Molecular knowledge of normal gastric tissues and gastric cancers remains incomplete. Here, we used single-cell RNA-seq to study the cell diversity of gastric tissues and gastric cancers. The expression landscape of normal gastric cell types and several candidate stem cell markers were obtained. Surprisingly, nearly all cell types in the antrum could transdifferentiate to intestinal metaplasia (IM). We also explored intra-tumoral heterogeneity and identified four common features of gastric cancer. In addition, we classified tumor cells into three major subtypes, which are associated with their prognosis. Finally, the proportions of mesenchymal and endothelial cells in the tumor microenvironment (TME) were negatively correlated with the prognosis of gastric cancer. Therefore, our work provides comprehensive molecular characterizations of both gastric development and gastric cancer at single-cell resolution and has significant potential to inspire better treatment strategies for gastric cancer.

正常胃组织与胃癌的分子认知仍有待完善。本研究采用单细胞RNA测序（single-cell RNA-seq）技术解析胃组织与胃癌的细胞多样性，成功构建正常胃细胞类型的表达图谱，并筛选出多个候选干细胞标志物。令人意外的是，胃窦内几乎所有细胞类型均可转分化为肠上皮化生（intestinal metaplasia, IM）。本研究同时探究了肿瘤内异质性，鉴定出胃癌的四类共性特征；此外，我们将肿瘤细胞划分为三大亚型，各亚型均与患者预后密切相关。最后，我们发现肿瘤微环境（tumor microenvironment, TME）中间充质细胞与内皮细胞的占比，与胃癌患者预后呈负相关。综上，本研究以单细胞分辨率完成了胃发育与胃癌的全面分子特征解析，为优化胃癌治疗策略提供了重要参考与潜在应用前景。

搜集汇总

背景与挑战

背景概述

该数据集通过单细胞RNA测序技术全面表征了胃组织和胃癌的分子特征，揭示了胃窦细胞转分化为肠化生的能力，并识别了胃癌的细胞亚型和预后相关因素。数据集包含10个样本，数据量为181.24 GB，为胃癌治疗策略的优化提供了重要参考。