摘要
目的:探讨乳酸化在胃癌(gastric cancer,GC)中的作用及其对预后的影响。方法:从癌症基因组图谱(TCGA)数据库收集GC患者的相关数据,结合基因集富集分析(GSEA)数据库及相关文献获取乳酸化相关基因(lactylation-related genes,LRGs)。筛选与乳酸化相关的GC差异基因,使用单因素Cox回归分析筛选影响GC预后的LRGs。利用Lasso回归构建乳酸化相关的预后风险模型,通过生存分析和ROC曲线评估该模型的预测效果。结合预后模型和临床病理特征,建立列线图。探讨该预后模型与肿瘤微环境、免疫细胞浸润以及药物敏感性之间的关系。最后,通过qRT-PCR分析和免疫组织化学染色实验验证预后基因在GC组织和正常组织中的表达差异。结果:识别出15个与预后相关的乳酸化差异基因(lactylation-related DEGs,LRDEGs),并基于其中9个关键乳酸化基因构建了预后风险模型,该模型在预测GC患者的总体生存方面表现良好(P<0.01)。高低风险组在肿瘤微环境、免疫细胞浸润及药物敏感性方面亦呈显著性差异(P<0.05)。qRT-PCR分析和免疫组织化学染色结果显示,SPP1和SLC5A12在GC组织中高表达(P<0.05)。结论:本研究构建的LRGs风险模型有望预测GC患者的预后,为临床个性化治疗提供新思路。
Objective:In this study,we examined the role of lactate in gastric cancer(GC)and its prognostic significance.Methods:Data obtained for gastric cancer patient were retrieved from The Cancer Genome Atlas(TCGA)database,and information pertaining to lactylationrelated genes(LRGs)was obtained by integrating data from the Gene Set Enrichment Analysis(GSEA)database and relevant literature.LRGs that are differentially expressed in GC were identified,and aunivariate Cox regression analysis was performed to identify those associated with the prognosis of GC patients.In addition,Lasso regression was applied to facilitate construction of a lactic acidosis-related prognostic risk model,whereas survival and receiver operating characteristic curve analyses were used to evaluate the predictive performance of the model.By integrating the prognostic model with clinicopathological characteristics,we also developed a nomogram and assessed the correlations of this prognostic model with the tumor microenvironment,immune cell infiltration,and drug sensitivity.Finally,quantitative realtime polymerase chain reaction(qRT-PCR)and immunohistochemical staining analyses were conducted to verify differences in the expression of prognostic genes in GC and adjacent normal tissues.Results:We identified fifteen prognosis-related differentially expressed lactylation-related genes(LR-DEGs),and successfully constructed a prognostic risk model based on nine of these genes,which showed excellent performance in predicting the overall survival of GC patients(P<0.01).Significant differences were also detected between high-and low-risk groups with respect to the tumor microenvironment,immune cell infiltration,and drug sensitivity(P<0.05).Furthermore,compared with normal tissues,the results of qRT-PCR analysis and immunohistochemical staining revealed the upregulated expression of SPP1 and SLC5A12 in GC tissues(P<0.05).Conclusions:We anticipate that the LRGs prognostic risk model established in this study will serve as a reliable tool for predicting the prognosis of gastric cancer patients and provide novel insights for the development of personalizedclinical treatment strategies.
作者
许建江
刘涛
王旭
马明礼
陈燕
姜雷
Jianjiang Xu;Tao Liu;Xu Wang;Mingli Ma;Yan Chen;Lei Jiang(The First Clinical College of Medicine,Lanzhou University,Lanzhou 730000,China;Department of General Surgery,The First Hospital of Lanzhou University,Lanzhou 730000,China;Department of Stomatology,The First Hospital of Lanzhou University,Lanzhou 730000,China;Department of Gastrointestinal Surgery,The First People's Hospital of Longnan,Longnan 746000,China)
出处
《中国肿瘤临床》
北大核心
2026年第2期78-84,共7页
Chinese Journal of Clinical Oncology
基金
甘肃省自然科学基金项目(编号:25JRRA1008)
兰州大学第一医院2023年院内基金项目(编号:ldyyyn2023-30,ldyyyn2025-168)资助。
关键词
乳酸化
胃癌
预后模型
免疫浸润
药物敏感性
lactylation
gastric cancer(GC)
prognostic model
immune infiltration
drug sensitivity
