Single-cell atlas of gastric cancer reveals malignant epithelial evolution and regulatory reprogramming of the tumor microenvironment

by Xiulan Li, Mengqi Guo, Yunhan Wen, Bo Long The inflammation–intestinal metaplasia (IM)–carcinoma cascade has been proposed as a framework for gastric cancer (GC) development, yet the cell-level heterogeneity and microenvironmental remodeling underlying this progression remain poorly characterized. Here, we constructed a single-cell transcriptomic atlas by integrating scRNA-seq data from chronic gastritis (superficial, CGS), IM, cancer-adjacent, and tumor tissues through a unified analytical pipeline.

Seven major cell lineages were resolved. Relative to CGS, IM and GC tissues exhibited a progressive contraction of epithelial compartments accompanied by expansion of immune and stromal populations.

Copy number variation (CNV) inference identified two tumor-restricted malignant epithelial subgroups—one biased toward differentiation and the other enriched for inflammatory and epithelial–mesenchymal transition (EMT) signatures—as well as putative proto-malignant intermediates that coexisted with phenotypically normal epithelium. Cell–cell communication analysis indicated broadly augmented crosstalk between epithelial cells and T cells, myeloid cells, and fibroblasts, with prominent involvement of a CD44–extracellular matrix (ECM) axis.