免疫相关lncRNA和胃癌预后关系分析及预测模型建立

Immune-related lncRNA and prognosis of gastric cancer:Relationship analysis and establishment of prediction model

目的研究免疫相关lncRNA与胃癌的关系,从而探索胃癌治疗潜在的靶点。方法通过TCGA数据库收集443例胃癌患者基因表达谱数据及临床数据,筛选胃癌中与免疫相关的lncRNA,通过单因素与多因素COX分析构建预测模型。采用Kaplan-Meier法进行生存分析,ROC曲线下面积(AUC)评价该模型预测的准确性,主成分分析(PCA)分析人群分布特征,ESTIMATE方法评估样品微环境中免疫细胞变化。结果本研究共获得546个免疫相关的lncRNA(相关系数Cor>0.4,P<0.001),通过单因素COX回归分析筛选出9个和胃癌预后相关的lncRNA,通过多因素COX分析最终筛选得到6个lncRNA(AP003392.1,AL022316.1,AC005586.1,LINC01315,AP001318.2,AL161785.1)并构建预测模型,模型将胃癌患者分为高风险与低风险组,生存分析提示两组间生存存在显著差异(P<0.001),ROC分析曲线下面积AUC为0.686,ESTIMATE分析提示高风险组的免疫细胞数量和基质细胞数量多,肿瘤纯度低,免疫评分高;而低风险组的免疫细胞数量和基质细胞数量较少,肿瘤纯度较高,免疫评分低,两者具有统计学差异(P<0.001)。结论免疫相关的lncRNA对胃癌患者具有潜在的预后价值,可能为胃癌的免疫学研究和治疗提供新的思路。

Objective To investigate the relationship between immune-related long noncoding RNA(lncRNA)and gastric cancer,so as to explore potential targets for the treatment of gastric cancer.Methods Gene expression profiles and clinical data of 443 patients with gastric cancer were obtained from TCGA database.Immune-related lncRNAs in gastric cancer were screened,and thereby a prediction model was constructed with univariate and multivariate COX analyses.Kaplan-Meier method was used for survival analysis,and area under the ROC curve(AUC)was used to evaluate the accuracy of model prediction.Principal component analysis(PCA)was used to analyze the distribution characteristics of the patients.ESTIMATE method was used to evaluate the changes of immune cells in the immune microenvironment.Results A total of 546 immune-related lncRNAs were obtained in this study(correlation coefficient Cor>0.4,P<0.001).Univariate COX regression screened up nine lncRNAs related to the prognosis of gastric cancer;of them,six lncRNAs(AP003392.1,AL022316.1,AC005586.1,LINC01315,AP001318.2,and AL161785.1)were finally obtained with multivariate COX analysis.Using these data,a predictive model was constructed,which classified gastric cancer patients into high-risk and low-risk groups.Survival analysis indicated a significant difference in survival between the two groups(P<0.001).The area under the ROC curve AUC was 0.686.ESTIMATE analysis indicated that the high-risk group had more immune cells and stromal cells,lower tumor cell purity,and higher immune scores,while the low-risk group had fewer immune cells and stromal cells,higher tumor cell purity,and lower immune scores,with statistical differences between groups(P<0.001).Conclusion Immune-related lncRNA can be potentially prognostic for patients with gastric cancer,and this may provide new ideas for immunological studies and treatment of gastric cancer.