Single‐cell characteristics and malignancy regulation of alpha‐fetoprotein‐producing gastric cancer
Yanxia Mei, Ming Li, Jihang Wen, Xiangxing Kong, Jun Li
Abstract
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.