Comprehensive analysis of scRNA-seq and bulk RNA-seq data via machine learning and bioinformatics reveals the role of lysine metabolism-related genes in gastric carcinogenesis

Abstract

Abstract Background Gastric cancer (GC) is a highly aggressive and heterogeneous cancer with extremely complex biological characteristics. Lysine and its metabolism are closely related to human cancer, but little is known about how lysine metabolism-related genes contribute to gastric carcinogenesis. Methods The roles of lysine metabolism-related genes in GC were investigated by in-depth analysis of single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data via machine learning and multiple bioinformatics methods and confirmed by multiple cell and molecular biology methods. Results By systematically analyzing the heterogeneity of GC cells and interactions among cell subtypes, two key genes, solute carrier family 7 member 7 (SLC7A7) and vimentin (VIM), were innovatively identified as lysine metabolism-related genes involved in gastric carcinogenesis. The potential functional mechanisms involved immune infiltration, signaling pathway regulation, drug sensitivity, molecular regulatory networks, tumor regulatory genes, and metabolic pathways. A reliable prognostic risk nomogram was established for GC prognosis prediction. Moreover, the expression of the lysine metabolism-related genes SLC7A7 and VIM and their effect on cellular phenotypes in gastric carcinogenesis were verified in clinical samples and in vitro experiments, including cell proliferation, migration, invasion and cell cycle assays. Conclusions We explored the role of lysine metabolism-related genes and prognostic models in GC with multiple datasets, providing novel metabolic targets.

Keywords

• Gastric cancer
• Lysine metabolism
• ScRNA-seq
• Bulk RNA-seq
• Machine learning
• Immune infiltration