基于线粒体基因构建非小细胞肺癌预后模型及肿瘤免疫微环境分析  

Construction of a prognostic model for non-small cell lung cancer based on mitochondrial genes and analysis of the tumor immune microenvironment

作　　者：李智 刀承欢 郭思佳[2] LI Zhi;DAO Cheng-huan;GUO Si-jia(Graduate School of Tianjin University of Traditional Chinese Medicine,Tianjin 300100,China;不详)

机构地区：[1]天津中医药大学研究生院,天津300100 [2]天津中医药大学第二附属医院

出　　处：《现代预防医学》2025年第3期398-405,共8页Modern Preventive Medicine

基　　金：国家自然科学基金项目(81403222,81874398)。

摘　　要：目的本研究旨在构建线粒体相关风险评估模型,探讨线粒体对非小细胞肺癌生存期的影响,预测免疫状态,并评估其潜在价值。方法分别从Mito Carta3.0数据库和癌症基因组图谱(cancer genome atlas,TCGA)数据库下载了线粒体和非小细胞肺癌相关数据,筛选出具有差异表达的线粒体相关基因,通过Cox回归分析构建风险评分模型,并根据风险评分的中位值将TCGA数据库中的非小细胞肺癌患者分为高风险组和低风险组。采用Kaplan-Meier分析、受试者工作特征曲线、临床病例特征分析及免疫状态评估来验证预后模型的有效性。结果在非小细胞肺癌样本中共获得320个线粒体相关基因,通过COX分析筛选出的4个关键模型基因(TIMM10、CYP24A1、BCL2L10、ACSM5),并构建非小细胞肺癌的列线图预测模型。免疫细胞浸润评估发现风险评分与T细胞、B细胞、巨噬细胞富集呈负相关;相反,而静息肥大细胞、癌症相关成纤维细胞及髓系祖细胞富集与风险评分正相关。高风险组患者的总生存期较短,并伴有更高水平的免疫抑制细胞浸润。IMvigor210免疫疗法模型验证发现在膀胱癌中高低风险组生存概率存在显著差异。结论本研究构建了一种线粒体基因风险评分模型,用于预测非小细胞肺癌的预后。TIMM10、CYP24A1、BCL2L10、ACSM5有望作为非小细胞肺癌后续研究的潜在靶点。Objective To construct a mitochondrial-related risk assessment model to explore the impact of mitochondria on the survival of patients with non-small cell lung cancer(NSCLC),predict immune status,and evaluate its potential value.Methods Mitochondrial and NSCLC-related data were downloaded from the MitoCarta3.0 database and The Cancer Genome Atlas(TCGA)database,respectively.Differentially expressed mitochondrial-related genes were screened,and a risk scoring model was constructed using Cox regression analysis.Based on the median risk score,NSCLC patients in the TCGA database were divided into high-risk and low-risk groups.The validity of the prognostic model was verified using Kaplan-Meier analysis,receiver operating characteristic(ROC)curves,clinical case feature analysis,and immune status assessment.Results A total of 320 mitochondrial-related genes were obtained from NSCLC samples.Four key model genes(TIMM10,CYP24A1,BCL2L10,ACSM5)were selected through COX analysis,leading to the construction of a nomogram prediction model for NSCLC.Immune cell infiltration assessment revealed a negative correlation between risk scores and the enrichment of T cells,B cells,and macrophages;conversely,the enrichment of resting mast cells,cancer-associated fibroblasts,and myeloid progenitor cells was positively correlated with risk scores.Patients in the high-risk group had shorter overall survival and exhibited higher levels of immune suppressive cell infiltration.Validation of the IMvigor210 immunotherapy model showed significant differences in survival probabilities between high-risk and low-risk groups in bladder cancer.Conclusion This study established a mitochondrial gene risk scoring model for predicting the prognosis of NSCLC.TIMM10,CYP24A1,BCL2L10,and ACSM5 are promising potential targets for further research on NSCLC.

关 键 词：非小细胞肺癌 线粒体 COX模型 免疫微环境 

分 类 号：R734.2[医药卫生—肿瘤]