基于代谢相关基因的胃癌预后模型的构建和验证  

Construction and validation of a prognostic model based on metabolism-related genes for patients with gastric cancer

作　　者：杨永[1] 张蕾 舒鹏 YANG Yong;ZHANG Lei;SHU Peng(Clinical Laboratory,the First Affiliated Hospital of Ningbo University,Ningbo 315000,China;不详)

机构地区：[1]宁波大学附属第一医院检验科,315000 [2]宁波市北仑区人民医院分子实验室

出　　处：《浙江医学》2024年第4期347-353,I0004,共8页Zhejiang Medical Journal

基　　金：浙江省病理生理学技术研究重点实验室开放基金(201914)。

摘　　要：目的 整合胃癌(GC)分子亚型和代谢相关基因,并依此构建GC预后模型。方法 从基因综合表达(GEO)数据库中采集GC患者基因表达谱和临床数据,通过整合网络分析筛选出主调控上皮间质转化(EMT)亚型的代谢标志基因,再通过Cox比例风险回归整合标志基因与生存信息,构建基于代谢相关基因的GC预后模型;依据该模型对GC患者进行风险分层,采用Kaplan-Meier生存曲线评估模型的预后预测作用,通过基因集富集分析(GSEA)筛选富集的通路。结果 整合网络分析筛选出3个主调控EMT亚型的代谢标志基因,分别为人脂质磷酸磷酸酶相关蛋白4型基因、谷氨酸胺-果糖-6-磷酸转氨酶2基因和硫酸酯酶1基因;基于这3个代谢标志基因构建的预后模型可将GC患者划分为高危组和低危组。生存曲线分析表明,高危组患者的预后更差,在多组验证数据集中均呈现一致结果,该模型表现出较强的预后预测效能。GSEA分析表明,高危组中转化生长因子-β信号传导、EMT等与癌恶性特征相关的通路显著富集;M2巨噬细胞、M0巨噬细胞及中性粒细胞浸润与高风险显著相关。结论 基于代谢相关基因的GC预后模型可实现GC患者风险分层,有助于指导GC患者的精准治疗。Objective To construct and varify a prognostic model based on metabolism-related genes for patients with gastric cancer(GC).Methods Transcriptomic data and clinical information of GC patients were obtained from the gene expression omnibus(GEO) database.Integrated network analysis was conducted to identify key metabolism-related genes that regulate the epithelial-mesenchymal transition(EMT) subtype of GC.A metabolism-related prognostic model for GC was constructed using Cox regression,and risk stratification of GC patients was performed according to this model.The Kaplan-Meier survival curve was used to evaluate the prognostic prediction of the model,and gene set enrichment analysis(GSEA)was used to assess the inherent biological significance of the model.Results Integrated network analysis identified 3 metabolism marker genes(phospholipiol phosphatase related 4,glutamine-fructose-6-phosphate transaminase 2,and sulfatase 1) that were the main regulators of the EMT subtype,based on which a prognostic model was developed.According to the model,GC patients were classified as high-risk and low-risk groups.The Kaplan-Meier survival curves showed that patients in the high-risk group had a worse prognosis,and consistent results were observed in multiple validation datasets.GSEA analysis showed that pathways associated with malignant features such as TGF-β signaling and EMT were significantly enriched in the high-risk group;in addition,high-risk group is also significantly associated with the infiltration of M2 macrophages,M0 macrophages,and neutrophils.Conclusion A risk prediction model based on metabolism-related genes has been developed in the study,which may be used for predict the prognosis of gastric cancer patients.

关 键 词：胃癌 预后 代谢 标志物 

分 类 号：R735.2[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]