Research Finds Link Between Inflammation and Early Gastric Cancer

Early gastric cancer arises from a highly coordinated microenvironmental state driven by inflammation, new research has found.

Early gastric cancer represents a critical yet biologically poorly understood stage of gastric carcinogenesis. Although the progression from chronic gastritis to atrophic gastritis, intestinal metaplasia, and eventually carcinoma is well established, most existing studies have focused on individual cell types or isolated molecular events. These reductionist approaches do not fully explain why tumour initiation preferentially occurs within specific spatial contexts or how inflammation, epithelial plasticity, and the immune microenvironment interact.

A new study published online in the Chinese Medical Journal on 7th August 2026 addresses this gap. Led by Professor Wang Chuanxin of Shandong University, the research team integrated single cell RNA sequencing with spatial transcriptomics to systematically map the cellular composition and spatial transcriptional architecture across non atrophic gastritis, atrophic gastritis, and early gastric cancer.

The original paper is titled Spatial remodeling of inflammatory niches drives stemness acquisition and malignant transformation during early gastric tumourigenesis. Human tissue samples spanning the disease trajectory were analysed to construct a spatially resolved transcriptional atlas of gastric carcinogenesis at its most biologically ambiguous stage.

The investigators demonstrate for the first time that early gastric cancer arises within a highly coordinated microenvironmental state driven by inflammation, which they define as an inflammation associated spatial niche.

The niche is characterised by the selective maintenance of epithelial stem like programmes, enhanced inflammatory chemotactic signalling that recruits immune cells, and regional enrichment of immunosuppressive cell populations at sites of premalignant epithelium.

Mechanistically, the team identifies the SOX9 CXCL axis as a key downstream regulatory module within the inflammatory spatial niche. This axis links epithelial stemness maintenance to macrophage recruitment and immune microenvironment remodelling.

SOX9, a transcription factor involved in development and stem cell maintenance, acts as a downstream effector, connecting to CXCL family chemokines that serve as ligands for CXCR2 receptors on myeloid cells. The researchers propose that this interaction links epithelial stemness to macrophage recruitment, helping reshape the local immune environment towards a tumour permissive configuration.

Concurrent targeting of CXCR2 and CSF1R mediated pathways effectively disrupts the structural integrity of the inflammatory niche. The paper reports that this dual intervention significantly suppresses early gastric cancer progression in xenograft models. CXCR2 blockade interrupts the recruitment of tumour promoting myeloid cells, while CSF1R inhibition undermines the maintenance of macrophages already present in the tissue.

Conceptually, the study presents the spatial niche as a fundamental regulatory unit for understanding early gastric cancer initiation, moving beyond isolated single cell or single gene events.

Clinically, the findings provide a novel framework for early gastric cancer risk stratification and intervention. Targeting inflammation associated spatial niches rather than isolated tumour cell populations may enable earlier therapeutic strategies.

Current surveillance of patients with atrophic gastritis and intestinal metaplasia relies largely on histological grading and endoscopic detection. Identifying these niches through spatially resolved biomarkers or targeted biopsy could provide a more precise indicator of regions at risk of malignant transformation.

Gastric cancer remains a major global health challenge, with progression from chronic inflammation to malignancy occurring in only a minority of affected individuals. By revealing a discrete, targetable spatial state that precedes overt neoplasia, the research offers a new lens on prevention. Further experimental validation and clinical testing of the CXCR2 and CSF1R targeting approach will be required.

The findings suggest that early gastric cancer development is shaped by an inflammation associated niche that maintains stemness, recruits macrophages, and locally suppresses immune surveillance.

Professor Chuanxin is a Tier 2 Professor at Shandong University and a Doctoral Supervisor whose research focuses on tumour biomarkers and early cancer diagnosis. The study was supported by grants including the National Key Research and Development Program of China and the National Natural Science Foundation of China.