Single-cell RNA Sequencing Demonstrates the Heterogeneity of Different Molecular Subtypes in Gastric Cancer.

ABSTRACT

Gastric cancer is a disease with high molecular and phenotypic heterogeneity. We integrated 119,878 cells from different molecular subtypes of gastric cancer and conducted comprehensive analysis. We found that patients with different molecular subtypes of gastric cancer showed significantly different cell composition heterogeneity, and the proportion of plasma cells was higher in GS tumors. After that, we constructed subtype-specific lncRNA-gene regulatory networks and identified subtype-specific lncRNA-related biological functions and pathways. Our study found that MALAT1-CTNNB1 regulatory pairs existed in CIN subtype, XIST-KLF2 regulatory pairs existed in GS subtype, and KCNQ1OT1-CCND2 regulatory pairs existed in MSI subtype. Next, we identified subtype-specific lncRNAs associated with prognosis. Our study found that NEAT1 could be used as prognostic factors for CIN tumors, and MALAT1 and XIST could be used as prognostic factors for GS tumors. In addition, we characterized the interactions between tumor cells and tumor microenvironment cells in different molecular subtypes of gastric cancer. In conclusion, we revealed the heterogeneity among different TCGA molecular subtypes of gastric cancer at the single-cell level, and identified the subtype-specific lncRNAs associated with prognosis. Our study may contribute to the in-depth understanding of the heterogeneity of gastric cancer and the prediction of patient prognosis.