结核通路基因与肺鳞状细胞癌预后及免疫微环境的相关性研究  

The correlation between tuberculosis pathway genes and the prognosis and immune microenvironment of lung squamous cell carcinoma

作　　者：蒋逆立 张蝶 刘曾晶 胡艳玲 Ni-Li JIANG;Die ZHANG;Zeng-Jing LIU;Yan-Ling HU(Life Science Institutes,Guangxi Medical University,Nanning 530022,China;Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry,Guangxi Medical University,Nanning 530021,China;School of Information and Management,Guangxi Medical University,Nanning 530022,China)

机构地区：[1]广西医科大学生命科学研究院,南宁530022 [2]广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心,南宁530021 [3]广西医科大学信息与管理学院,南宁530022

出　　处：《数理医药学杂志》2023年第9期641-649,共9页Journal of Mathematical Medicine

基　　金：广西重点研发计划项目(桂科AB22035027)。

摘　　要：目的探索结核通路相关基因表达差异与肺鳞状细胞癌(lung squamous cell carcinoma,LUSC)预后及肿瘤免疫微环境的关系,判别结核合并LUSC的预测基因和免疫因子,寻找新的治疗靶点。方法基于京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)获取结核相关通路(map05152)基因。利用癌症基因组图谱数据库(The Cancer Genome Atlas,TCGA),纳入374例LUSC患者的基因表达谱,并进行归一化处理。构建COX比例风险回归模型并通过受试者工作特征(receiver operating characteristic,ROC)曲线进行验证,利用列线图分析LUSC患者的预后,并分析结核通路基因在不同风险分组的肿瘤微环境和单样本免疫浸润富集差异。结果CASP9、FADD、PLK3基因与LUSC预后相关。风险评分高的患者更容易出现免疫细胞浸润富集差异,尤其是central memory CD4 T、effector memeory CD4 T、gamma delta T、natural killer和natural killer T等免疫细胞呈低富集状态。结论CASP9、FADD、PLK3基因可用于评估LUSC患者的预后,并根据风险评分识别肿瘤免疫微环境的变化。对于高风险组有富集差异的免疫细胞,未来有望进一步研究并发现结核合并LUSC潜在的治疗靶点。Objective To explore the relationship between differential expression of genes related to the tuberculosis pathway and the prognosis and tumor immune microenvironment of lung squamous cell carcinoma(LUSC),and identify predictive genes and immune factors for tuberculosis combined with LUSC,and to find new therapeutic targets.Methods The pathway(map05152)genes related to the tuberculosis were obtained based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)database.The gene expression profiles of 374 LUSC patients from The Cancer Genome Atlas(TCGA)database were enrolled and normalized.The COX proportional hazards model was constructed and validated by receiver operating characteristic(ROC)curve.The Nomogram was used to analyze the prognosis of LUSC patients in different risk subgroups.Finally,the differences between tumor microenvironment and single sample immune infiltration enrichment caused by tuberculosis pathway genes in different risk subgroups were analyzed.Results The CASP9,FADD,PLK3 genes were correlated with the prognosis of LUSC.Patients with high risk scores were more likely to experience differences in immune cell infiltration and enrichment,especially,these important immune cells:central memory CD4 T,effector memory CD4 T,gamma delta T,natural killer,and natural killer T presented a low enrichment state.Conclusion CASP9,FADD and PLK3 genes can be used to evaluate the prognosis of LUSC patients and identify the changes in tumor immune microenvironment based on risk scores.Potential therapeutic targets could be identified for LUSC and tuberculosis patients by targeting immune cells with enriched differences in high risk group.

关 键 词：结核 肺鳞状细胞癌 基因 免疫 TCGA 预后 列线图 

分 类 号：R734.2[医药卫生—肿瘤]