The stomach is an important digestive organ with various biological functions. However, due to the complexity of its cellular and glandular composition, its precise cellular biology has yet to be elucidated. Our previous investigation, employing single-cell RNA sequencing, aimed to unravel the diversity of normal and metaplastic gastric mucosa. This exploration led to the identification of LEFTY1 as a marker for gastric epithelial stem cells and shed light on aberrant fibroblast expansion associated with metaplastic alterations [1].
Gastric cancer is the fifth leading cause of cancer deaths worldwide, with high incidence and mortality rates in East Asia including Japan. Therefore, clarifying the biology of gastric cancer is crucial for overcoming this disease. Building upon the previous work, our current study is to delineate the function of LEFTY1 and elucidate the interplay between tumor cells and the aforementioned fibroblasts in gastric cancer. Employing spatial transcriptome analysis at single-cell resolution, we sought to identify intricate interactions between these tumor cells and stromal cells. Through the application of bioinformatics methods, we delineated various niches corresponding to pathological structures such as lymph follicles, tumor microinvasions, and the interface between normal and tumor cells. Furthermore, we conducted single-cell level classification, encompassing the annotation of tumor cells, fibroblasts, and other immune cells.
Our study initially elucidated the spatial distribution pattern in gastric cancer at this scale, and our spatial transcriptome analyses furnish novel insights into cancer biology and carcinogenesis.