Early gastric cancer (EGC) represents the most critical yet biologically least understood stage in gastric carcinogenesis. Although the pathological progression from chronic gastritis to atrophic gastritis, intestinal metaplasia, and eventually carcinoma has been well established, most existing studies have focused on individual cell types or isolated molecular events. Such reductionist approaches fail to explain why tumor initiation preferentially occurs within specific spatial contexts and lack a systematic understanding of the coordinated interplay among inflammation, epithelial plasticity, and the immune microenvironment.
By integrating single-cell RNA sequencing with spatial transcriptomics, this study systematically delineates the cellular composition and spatial transcriptional architecture across non-atrophic gastritis, atrophic gastritis, and early gastric cancer. At the spatial level, we demonstrate for the first time that early gastric cancer arises from an inflammation-driven, highly coordinated spatial microenvironmental state. We define this state as an inflammation-associated spatial niche, characterized by the selective maintenance of epithelial stem-like programs, enhanced inflammatory chemotactic signaling, and the regional enrichment of immunosuppressive cell populations. The study was published online in Chinese Medical Journal on August 07, 2026.
Mechanistically, we identify the SOX9-CXCL axis as a key downstream regulatory module within the inflammatory spatial niche, linking epithelial stemness maintenance to macrophage recruitment and immune microenvironment remodeling. Furthermore, we demonstrate that concurrent targeting of CXCR2- and CSF1R-mediated pathways effectively disrupts the structural integrity of the inflammatory niche, thereby significantly suppressing early gastric cancer progression.
Conceptually, this study introduces the spatial niche as a fundamental regulatory unit for understanding early gastric cancer initiation, moving beyond traditional paradigms centered on single-cell or single-gene events. Methodologically, it highlights the unique value of integrative spatial multi-omics approaches in resolving complex inflammation-to-tumor progression trajectories. Clinically, our findings provide a novel framework for early gastric cancer risk stratification and intervention, suggesting that targeting inflammation-associated spatial niches, rather than isolated tumor cell populations, may enable earlier and more precise therapeutic strategies.
Collectively, this work establishes an important theoretical foundation and potential translational direction for early gastric cancer prevention and spatial microenvironment-oriented therapies.
Reference
Title of original paper: Spatial remodeling of inflammatory niches drives stemness acquisition and malignant transformation during early gastric tumorigenesis
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/CM9.0000000000004203
About Professor Wang Chuanxin from Shandong University
Professor Wang Chuanxin is a Tier-2 Professor at Shandong University and a Doctoral Supervisor. He has long been dedicated to research on tumor biomarkers and early cancer diagnosis. As the first inventor, he has been granted 23 national invention patents. As corresponding author, he has published more than 200 SCI-indexed papers in journals such as Molecular Cell , Nature Communications , and Cell Death & Differentiation , and has been recognized for consecutive years as a Highly Cited Chinese Researcher in the field of Clinical Medicine.
Funding information
This work was supported by grant from The National Key Research and Development Program of China [2023YFC2413200], the National Natural Science Foundation of China [82327802，82472357], the Natural Science Foundation of Shandong Province [ZR2024MH107，ZR2023JQ027], Taishan Scholars Program of Shandong Province [NO.tspd20210323, NO.tsqn202211322, NO.tsqn202211323], Outstanding Young and Middle-aged Scholar of Shandong University, Shandong University Interdisciplinary Cultivation Program [2022JC002].
Chinese Medical Journal
Experimental study
Human tissue samples
Spatial remodeling of inflammatory niches drives stemness acquisition and malignant transformation during early gastric tumorigenesis
7-Aug-2026