Objective: To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
Methods: ScRNA-seq was performed on two tumors collected from patients with AFPGC. InferCNV and sub-clustering were applied to identify typical AFPGC cells, followed by AddModuleScore, pathway enrichment, Pseudo-time, and Scenic analyses. Data from a gastric cancer (GC) cohort were collected for conjoint analysis. The analytical results were verified by cell experiments and immunohistochemistry.
Results: AFPGC cells are similar to hepatocytes in transcriptome and transcriptional regulation, with kinetic malignancy-related pathways, compared to the common malignant epithelium. In addition, compared to common GC cells, malignancy-related pathways, such as epithelial-mesenchymal transition (EMT) and angiogenesis, were upregulated in AFPGC. Mechanistically, Dickkopf-1 (DKK1) was found to be associated with AFP expression and malignant phenotype upon combining our scRNA-seq data with a public database, which was further verified by a series of in vitro experiments and immunohistochemistry.
Conclusion: We demonstrated the single-cell characteristics of AFPGC and that DKK1 facilitates AFP expression and malignancy.
Keywords: Dickkopf-1; alpha-fetoprotein; alpha-fetoprotein-producing gastric cancer; gene expression omnibus; malignancy; molecular feature; single-cell RNA sequencing; the cancer genome atlas.
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.