Shao Yongfu, Chen Chujia, Yu Xuan, Yan Jianing, Guo Junming, Ye Guoliang
Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, 315020, China.
Health Science Center, Ningbo University, Ningbo, 315211, China.
BMC Cancer. 2025 Apr 9;25(1):644. doi: 10.1186/s12885-025-14051-w.
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.
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.
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.
We explored the role of lysine metabolism-related genes and prognostic models in GC with multiple datasets, providing novel metabolic targets.
胃癌（GC）是一种侵袭性很强且具有异质性的癌症，其生物学特性极其复杂。赖氨酸及其代谢与人类癌症密切相关，但赖氨酸代谢相关基因如何促进胃癌发生尚不清楚。
通过机器学习和多种生物信息学方法对单细胞RNA测序（scRNA-seq）和批量RNA测序（RNA-seq）数据进行深入分析，研究赖氨酸代谢相关基因在胃癌中的作用，并通过多种细胞和分子生物学方法进行验证。
通过系统分析胃癌细胞的异质性以及细胞亚型之间的相互作用，创新性地鉴定出两个关键基因，溶质载体家族7成员7（SLC7A7）和波形蛋白（VIM），它们是参与胃癌发生的赖氨酸代谢相关基因。潜在的功能机制涉及免疫浸润、信号通路调节、药物敏感性、分子调控网络、肿瘤调控基因和代谢途径。建立了一个可靠的预后风险列线图用于胃癌预后预测。此外，在临床样本和体外实验中验证了赖氨酸代谢相关基因SLC7A7和VIM的表达及其对胃癌发生中细胞表型的影响，包括细胞增殖、迁移、侵袭和细胞周期检测。
我们利用多个数据集探索了赖氨酸代谢相关基因和预后模型在胃癌中的作用，提供了新的代谢靶点。
