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bioRxiv · 10.1101/455121

A comprehensive analysis of single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer

Peng, Z.·Mingran, Y.·Yiding, Z.·Shuai, X.·Xinxing, L.·Aidi, T.·Shao, L.
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Abstract

Intestinal-type gastric cancer is preceded by premalignant lesions including chronic atrophic gastritis (CAG) and intestinal metaplasia (IM), which are characterized as changes in cell types. In this study, for the first time, we systematically constructed a single-cell atlas for a total of 31,164 high-quality cells from gastric mucosa biopsies of patients spanning a cascade of gastric premalignant lesions and early gastric cancer (EGC) using single-cell RNA sequencing (scRNA-seq). Based on the atlas, we construct a network underlying the changes of cellular and molecular characteristics of gastric epithelial cells across different lesions. We found the conversion of gland mucous cells (GMCs) toward a more intestinal-like stem cell phenotype during metaplasia, and identified OR51E1 as a novel marker for early-malignant enteroendocrine cells. We also found that HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Finally, we identified a panel of EGC-related specific signature, with clinical implications for the precise diagnosis of EGC. Our study offers unparalleled insights into the human gastric cellulome in premalignant and early-malignant lesions and provides an important data resource that will facilitate studies in gastritis-induced tumourigenesis and gastric cell biology.\n\nSignificance StatementUnderstanding cellular characteristics in gastric premalignant and malignant lesions would help us better understand the gastric cancer (GC) pathogenesis. In this paper, for the first time, we systematically constructed a single-cell transcriptome network of human premalignant gastric mucosa and early GC (EGC) and derived novel findings from it. We identified OR51E1 as a novel marker for early-malignant enteroendocrine cells and a panel of genes as the EGC-specific signature, with clinical implications for the precise diagnosis of EGC. We also found HES6 might mark a goblet cell subset that precede morphologically identifiable goblet cells in IM mucosa, potentially aiding the identification of metaplasia at the early stage. Our study provided an unprecedented data resource that will facilitate studies underlying gastritis-induced tumorigenesis.

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Peng, Z., Mingran, Y., Yiding, Z., Shuai, X., Xinxing, L., Aidi, T., Shao, L.. 2018-11-05. A comprehensive analysis of single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. https://doi.org/10.1101/455121

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