Single-Cell Transcriptomics Reveals Tumorigenic Lineages and Interactions Persisting and Evolving From Premalignancy to Cancer in the Stomach

In CTLA4-knockdown mouse gastric disease, a metaplastic/tumorigenic population emerges in premalignancy from chief-cell programs and persists into adenocarcinoma.

• Why it matters: Gastric cancer is usually detected late, yet the epithelial molecular changes during the premalignant window are not well mapped, limiting early detection.
• What they did: Single-cell RNA sequencing and 40-color spectral flow cytometry profiled gastric tissue across premalignant and cancer stages, integrating epithelial lineage and cell-cell communication analyses in mice and validating markers in human gastric adenocarcinoma.
• The result: Fibronectin (FN1) signaling increases from premalignancy to cancer, shifting from stromal to autocrine in the metaplastic/tumorigenic population; Embigin (EMB) rises at transcript and protein levels in premalignancy, remains elevated in cancer, co-expresses CD133, and is higher in human adenocarcinoma than matched normal tissue.

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