DOI: 10.3390/cells15212020 ISSN: 2073-4409

Decoding Cellular Complexity in the Gastric Precancerous Field: Spatial Evolution from Metaplastic Glands to Early Gastric Cancer

Jingwei Kang, Shigang Ding, Xingting Guo

Gastric precancer is conventionally staged as a linear histological sequence, but it develops within a patchy, continuously remodeling mucosa. This narrative review reframes gastric carcinogenesis as a multiscale spatial process in which epithelial states, clonal gland dynamics, immune–stromal neighborhoods, regional Helicobacter pylori (H. pylori) and non-H. pylori colonization, and metabolic or physicochemical gradients may jointly shape local risk. Gland-resolved studies show that metaplasia may expand through fission and remain clonally continuous with dysplasia in selected lesions, whereas broad genomic and epigenetic field alterations may also support independent tumor emergence. Single-cell and spatial analyses identify hybrid, stem-like, and proliferative epithelial states embedded within evolving multicellular niches, although most evidence remains cross-sectional and biased toward established cancer. We therefore propose a non-deterministic model in which injury drives gland loss and niche remodeling; metaplastic clones expand and diversify; local ecological pressures may select high-risk states; and only a minority of glands cross the neoplastic threshold. This remains a working hypothesis, particularly for niche-driven selection of human precancerous clones. Clinically, the framework is consistent with the prognostic value of metaplastic extent, corpus involvement, and the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems, while defining the longitudinal, topographically annotated, gland-resolved studies needed to determine whether spatial risk maps add clinical value beyond established staging.

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