Lineage-Specific Epithelial Responses in the Chronic Inflammation and Tumorigenesis of Gastric Cancer (PRJCA040096)
Gastric cancer is a group of inflammation-related cancer which remains vital worldwide. The sub-group of intestinal-type gastric adenocarcinoma is usually developed through well-characterized sequential pathological stages, from chronic gastritis, atrophy, intestinal metaplasia and dysplasia to in-situ carcinoma. Spasmolytic polypeptide-expressing metaplasia (SPEM) is a regenerative lesion in the gastric mucosa which is considered as a potential precursor to adenocarcinoma. However, the most likely cellular origin(s) of SPEM based on the effect of chronic inflammation remains controversial. In the current study, we developed a mouse model which progressed towards intestinal metaplasia and adenocarcinoma with N-methyl-N-nitrosourea feeding and chronic restraint stress stimulation, which can mostly reveal the true face of carcinogen and tumorigenesis in human being. Single-cell RNA sequencing technology was applied to compare the transcriptomic profiles between the pathological lesions with normal gastric mucosa, revealing that multiple epithelial lineages along the gland axis demonstrated plasticity and complicated reprogramming processes during chronic inflammation and tumorigenesis. SPEM is more representative for a specific cell state, rather than a distinct cell subgroup, and all epithelial linages could transform toward such state during tissue damage. Six differentially expressed markers were identified harboring prognostic potential and could be used for monitoring the pathological process.