基于TCGA数据库分析泛凋亡相关基因构建肺腺癌预后模型的预测价值及其对肿瘤免疫微环境的影响

Expression of PANoptosis-Related Genes in Predicting Prognosis of Patients with Lung Adenocarcinoma and Their Relation with Immune Microenvironment

[目的]探讨泛凋亡(PANoptosis)对肺腺癌(lung adenocarcinoma,LUAD)患者预后及免疫微环境的预测价值。[方法]从TCGA数据库下载LUAD样本与正常样本的基因表达谱及临床数据,从已发表的文献中获取PANoptosis相关基因并分析其在肿瘤组和对照组间的差异表达基因。通过单变量Cox分析和LASSO-Cox回归分析构建生存预后模型,将患者按风险评分划为高、低风险组。通过Kaplan-Meier生存曲线和受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)评价模型的预测性能,再对模型风险评分进行独立预后分析。GO和KEGG富集分析探索生物功能和潜在的信号通路。采用TIMER数据库ESTIMATE算法综合分析PANoptosis相关基因与免疫微环境相关性。通过qRT-PCR验证PANoptosis预后相关基因在LUAD组织和正常肺组织间的差异表达。[结果]共有15个PANoptosis相关基因在LUAD组和正常组间存在差异性表达,从中筛选出4个PANoptosis预后相关基因(RIPK3、NLRP3、FADD、MLKL)。在LASSO-Cox回归模型中,高风险组的生存率低于低风险组(P<0.001)。单变量和多变量Cox分析显示该评分模型是LUAD的独立预后因素(HR=2.179,95%CI:1.347~3.524,P=0.001),而GO和KEGG分析显示差异表达基因主要富集于与免疫相关的通路。高低风险组之间免疫微环境、免疫细胞差异和免疫检查点基因表达差异显著。此外,qRTPCR实验也证实PANoptosis相关基因FADD(P=0.007)和NLRP3(P<0.001)在LUAD组和正常组之间表达存在差异。[结论]本研究构建的PANoptosis相关基因的生存预后模型可以预测LUAD患者的预后及免疫微环境。

[Objective]To investigate the value of PANoptosis in predicting the prognosis of patients with lung adenocarcinoma(LUAD)and its relation with immune microenvironment.[Methods]Gene expression profiles and clinical data of lung adenocarcinoma(LUAD)samples and normal lung tissue samples were downloaded from the TCGA database,and PANoptosis-related genes were obtained from the published literature and analyzed for differences in expression between tumor and control groups.A survival prognostic model was constructed by univariate Cox analysis and Lasso Cox regression analysis,and patients were classified into high and low risk groups according to risk scores.The predictive value of the model was evaluated by Kaplan-Meier survival curves and time dependent receiver operating characteristic(ROC)curve.GO and KEGG enrichment analyses were performed to explore biological functions and potential signaling pathways of expression of PANoptosis-related genes.The TIMER database and ESTIMATE algorithm were used to analyze the correlations between PANoptosis-related genes and immune microenvironment.The differential expression of PANoptosis-related genes between LUAD tissues and normal lung tissues were verified by qRT-PCR.[Results]A total of 15 PANoptosis-related genes were differentially expressed between the LUAD and normal groups,from which 4 PANoptosis prognostic regulators(RIPK3,NLRP3,FADD,MLKL)were screened out.A predictive model for prognosis of LUAD patients was constructed,and the survival rate was lower in patients with high risk scores than that with low risk scores(P<0.001).Univariate and multivariate Cox analyses revealed that the survival prognostic model score was an independent prognostic factor for LUAD(HR=2.179,95%CI:1.347~3.524,P=0.001).While GO and KEGG analyses revealed that differentially expressed genes were mainly enriched in immune-related pathways.Significant differences in im-mune microenvironment,immune cell differences,and immune checkpoint gene expression were observed between high and low risk groups.In addition,qRT-PCR results also confirmed that PANoptosis-related genes FADD(P=0.007)and NLRP3(P<0.001)were differentially expressed between the LUAD tissue and the normal lung tissue.[Conclusion]A survival prognostic model constructed based on PANoptosis-related genes could predict the prognosis of patients with lung adenocarcinoma,which may be associated with immune microenvironment.