肺腺癌预后相关坏死性凋亡基因标志物的构建及验证  

Construction and Validation of Necroptosis Gene Marker Correlated with Prognosis of Lung Adenocarcinoma

作　　者：罗亭 欧阳锦 余石群 曾凡凡 高丽云 黄邵鑫[2] 汪鑫[2] LUO Ting;OU YANG Jin;YU Shi-qun;ZENG Fan-fan;GAO Li-yun;HUANG Shao-xin;WANG Xin(Public Health School of Nanchang University,Jiangxi Provincial Key Laboratory of Preventive Medicine,Nanchang 330006,China;Precision Preventive Medicine Laboratory of Basic Medical School,Jiujiang University,Jiujiang 332000,China)

机构地区：[1]南昌大学公共卫生学院,江西省预防医学重点实验室,南昌330006 [2]九江学院基础医学院精准预防医学实验室,江西九江332000

出　　处：《南昌大学学报（医学版）》2022年第5期1-7,24,共8页Journal of Nanchang University：Medical Sciences

基　　金：国家自然科学基金(81360447);江西省自然科学基金(20202BAB206067,20192ACB20019);中国博士后科学基金项目(2019M652334)。

摘　　要：目的构建肺腺癌(LUAD)预后相关坏死性凋亡基因标志物并对其进行评估。方法KEGG数据库筛选坏死性凋亡相关基因(NRGs);TCGA和GEO数据库中分别下载LUAD样本和正常样本的RNA测序及其相应临床数据,并以TCGA数据集作为训练队列,以GEO数据集作为验证队列,对筛选的NRGs进行差异和功能富集分析;单因素Cox及Lasso Cox回归分析构建NRGs的LUAD预后标志物;采用Kaplan-Meier生存分析、timeROC分析、多因素Cox回归分析和临床列线图评估该预后标志物;以GEO数据集(GSE31210)外部验证该预后标志物。结果筛选获得159个NRGs;在训练队列中鉴定出26个差异表达的NRGs(DENRGs);富集分析发现DENRGs主要参与坏死性凋亡和NOD样受体等信号通路;构建由6个NRGs(PLA2G4F、IL33、TLR4、RNF103.CHMP3、ALOX15、IL1A)组成的预后标志物;生存分析显示高风险组总体生存率(OS)明显低于低风险组(log-rank P<0.001);该预后标志物预测1年、3年和5年OS的AUC分别为0.672、0.631和0.624,且与LUAD患者OS显著相关(HR:2.30,95%CI:1.30~4.00,P<0.01);建立的列线图能较好地预测LUAD患者的生存;验证队列的分析结果与训练队列一致。结论成功构建一种新的NRGs预后标志物,其可用于预测LUAD患者的预后,且该预后标志物的预测能力良好。Objective To construct and evaluate necroptosis gene marker associated with the prognosis of lung adenocarcinoma(LUAD).Methods Necroptosis-related genes(NRGs)were screened from the KEGG database.The RNA sequencing and corresponding clinical data of LUAD patients were downloaded from TCGA and GEO databases.The TCGA dataset was used as the training cohort for differential analysis and functional enrichment of the selected NRGs.Univariate Cox and Lasso Cox regression were used to establish prognostic marker for LUAD in NRGs.Kaplan-Meier survival analysis,timeROC analysis,multivariate Cox regression analysis,and clinical nomogram were used to evaluate the marker.The GEO dataset(GSE31210)was used as the validation cohort for external validation of this marker.Results A total of 159 NRGs were obtained.Among them,26 differentially expressed NRGs(DENRGs)were identified in the training cohort.Enrichment analysis found that DENRGs mainly participated in necroptosis,NOD-like receptors and other signaling pathways.The prognostic marker consisted of 6 NRGs(PLA2G4F,IL33,TLR4,RNF103.CHMP3,ALOX15,and IL1A).Survival analysis showed the high-risk group had a lower overall survival(OS)rate than the low-risk group(log-rank P<0.001).The AUCs of the prognostic marker were 0.672,0.631 and 0.624 for predicting 1-,3-and 5-year OS,respectively.Multivariate Cox regression analysis showed that the prognostic marker was significantly correlated with the OS of LUAD patients(HR:2.30,95%CI:1.30-4.00,P<0.01).The established nomogram showed excellent potential for predicting survival in patients with LUAD.The analysis results of the validation cohort were consistent with those of the training cohort.Conclusion A novel necroptosis gene marker has been successfully constructed.It can be used to predict the prognosis of LUAD patients with favorable predictive power.

关 键 词：肺腺癌 坏死性凋亡 预后 标志物 

分 类 号：R734.2[医药卫生—肿瘤]