摘要
目的 通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库,构建肺腺癌中铁死亡相关的长链非编码RNA(long non-coding RNA,Lnc RNA)的预后模型,并对模型中的高风险组和低风险组患者进行免疫相关性分析。方法 在TCGA数据库中获取肺腺癌肿瘤组织及正常肺组织的基因表达数据及临床数据,筛选出铁死亡相关的差异LncRNA。采用Cox风险回归模型筛选并建立LncRNA预后风险预测模型,根据模型对患者进行评分并对高风险组和低风险组免疫相关功能进行比较。结果 共得到55个铁死亡预后相关的差异LncRNA,基于Cox回归分析结果构建了由16个LncRNA的多因素预后风险预测模型。患者风险评分高提示预后差。高风险组的树突状细胞、B淋巴细胞、肥大细胞等免疫细胞浸润程度,抗原呈递细胞(antigen-presenting cells,APC)共抑制、APC共刺激、趋化因子受体、免疫检查点等免疫功能以及IDO2、HHLA2、CD276、BTLA等免疫检查点相关基因表达均与低风险组不同(均P <0.05)。结论 基于16个铁死亡相关LncRNA的预后模型可以对肺腺癌患者的预后进行预测,且研究中得到的参与模型构建的铁死亡相关LncRNA可能与免疫浸润水平有关,有望成为免疫检查点抑制剂治疗的新靶点。
Objective To construct a prognostic model of ferroptosis-related long non-coding RNA(LncRNA)in lung adenocarcinoma using the cancer genome atlas(TCGA)cancer database,and to analyze the immune correlation between high and low risk patients in the model.Method The gene expression data and clinical data of lung adenocarcinoma tumor tissue and normal lung tissue were obtained from the TCGA database,and the differential LncRNA related to ferroptosis were screened out.Single and multivariate Cox risk regression models were used to screen and establish LncRNA prognostic risk prediction models.Patients were scored according to the model and immune-related functions were compared between high risk group and low risk group to derive immune-related differences between high risk group and low risk group.Result A total of 55 differential LncRNA related to the prognosis of ferroptosis were obtained.Based on the results of univariate and multivariate Cox regression analysis,a multivariate prognostic risk prediction model of 16 LncRNA was constructed.A high patient risk score indicated a poor prognosis.Immune correlation analysis showed that in high risk group and low risk group:dendritic cells,B lymphocyte,mast cells and other immune cells,antigen-presenting cells(APC)co-suppression,APC co-stimulation,chemokine receptors,immune checkpoints and other immune cells function,IDO2,HHLA2,CD276,BTLA and other immune checkpoint-related genes had significant statistical differences(all P<0.05).Conclusion The prognostic model based on 16 ferroptosis-related LncRNA can predict the prognosis of patients with lung adenocarcinoma,and the ferroptosis-related LncRNA involved in the model construction obtained in the study may be related to the level of immune infiltration,and are expected to be used as the new target of immune checkpoint inhibitor therapy.
作者
阮鑫
冯宇
陈海锐
吴柳盛
刘奇
周树德
张晋源
何炽准
余振东
刘继先
彭旭兴
李小强
Ruan Xin;Feng Yu;Chen Hairui;Wu Liusheng;Liu Qi;Zhou Shude;Zhang Jinyuan;He Chizhun;Yu Zhendong;Liu Jixian;Peng Xuxing;Li Xiaoqiang(Department of Thoracic Surgery,Peking University Shenzhen Hospital,Shenzhen 518036,Guangdong,China;Department of Blood Transfusion,Peking University Shenzhen Hospital,Shenzhen 518036,Guangdong,China)
出处
《肿瘤综合治疗电子杂志》
2024年第1期93-103,共11页
Journal of Multidisciplinary Cancer Management(Electronic Version)
基金
深圳市科技创新委员会资助项目(JCYJ20190809104601662,JCYJ20170816105345191)。
关键词
肺腺癌
铁死亡
长链非编码RNA
预后模型
免疫治疗
免疫检查点抑制剂
Lung adenocarcinoma
Ferroptosis
Long non-coding RNA
Prognostic model
Immunotherapy
Immune checkpoint inhibitor
