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Single-cell characteristics and malignancy regulation of alpha-fetoprotein-producing gastric cancer.
- Source :
- Cancer Medicine; May2023, Vol. 12 Issue 10, p12018-12033, 16p
- Publication Year :
- 2023
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20457634
- Volume :
- 12
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Cancer Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 164794712
- Full Text :
- https://doi.org/10.1002/cam4.5883