Single-cell characterization revealed hypoxia-induced metabolic reprogramming of gastric cancer

Abstract

Introduction: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Single-cell sequencing technology can achieve an accurate and unbiased assessment of cell heterogeneity. Therefore, it is necessary to explore the molecular characteristics of GC-related malignant cells at a single-cell resolution. Methods: Single-cell RNA sequencing GC profiles were collected from the Gene Expression Omnibus database. Moreover, feature gene sets of metabolic pathways and hypoxia signals were collected from the Molecular Signatures Database. The marker genes of specific cell types were collected from the published literature and CellMarker database. The R package InferCNV was used to calculate the copy-number variations of cells and to identify real cancer cells. The weighted relative pathway activity algorithm was used to evaluate the differences in metabolic activity between cell types. Results: Our study found that cancer epithelial cells exhibited individual differences in molecular features and showed metabolic heterogeneity. Oxidative phosphorylation and glycolytic pathway activity were the major contributors to the metabolic heterogeneity of cancer epithelial cells. Furthermore, we used the hypoxia signaling pathway to indirectly evaluate the oxygen content of cells and found that hypoxia contributed to the heterogeneity of cancer epithelial cells. Finally, functional identification of genes co-expressed with HIF1A showed that the reprogramming of the oxidative stress response contributed to the tumor malignant progression. Conclusions: This study described hypoxia-induced metabolic reprogramming of GC at a single-cell level, partially addressing the lack of insight into the heterogeneity of cancer cell metabolism when using traditional sequencing technology.

Keywords

• Single-cell RNA-Seq
• Gastric cancer
• Epithelial cell
• Metabolic reprogramming
• Hypoxia