标题：FGF2、CYSLTR1、RSAD2和HLA-DRA的表达水平与弥漫性大B细胞淋巴瘤预后的相关性

      作者：刘利，李珊珊，余楚壬，袁玉，代怀杰，曹培杰    东莞市厚街医院肿瘤血液科，广东 东莞 523945

      卷次： 2021年32卷15期

      【摘要】 目的 探讨免疫相关基因FGF2、CYSLTR1、RSAD2和HLA-DRA的表达水平与弥漫性大B细胞淋巴瘤(DLBCL)患者预后的相关性。方法 分别从基因表达综合(GEO)和癌症基因组图集(TCGA)数据库中获得221例和48例DLBCL患者的核糖核酸(RNA)测序数据。应用单因素和多因素COX回归模型以及Kaplan-Meier曲线探索免疫相关基因的表达水平与DLBCL患者总体生存(OS)的相关性。同时，应用时间依赖性接收器工作特性曲线(ROC)评估危险分层的性能。结果 单因素COX回归模型分析提示，总共有 4个免疫相关基因FGF2, CYSLTR1,RSAD2和HLA-DRA的高表达与DLBCL患者的不良OS显著相关[风险比(HR)>1，P<0.05]，此结果在Kaplan-Meier曲线中得到验证(P<0.05)；多因素COX回归模型被进一步用于对这4个免疫基因进行联合分析，发现FGF2对OS的贡献度最大(系数β=0.27)，并且可以对DLBCL患者进行危险分层；此外，单因素和多因素COX回归分析发现，危险分层是DLBCL患者独立的预后影响因子(P<0.05)；同时，进一步的时间依赖性ROC曲线表明危险分层具有较好的性能 [曲线下面积(AUC)>0.8]。结论 FGF2、CYSLTR1、RSAD2和HLA-DRA的高表达与DLBCL患者的不良预后显著相关，同时，联合这四个免疫相关基因可以对DLBCL患者进行危险分层。
      【关键词】 弥漫性大B细胞淋巴瘤；免疫相关基因；总体生存；危险分层；分子标志物
      【中图分类号】 R733.4 【文献标识码】 A 【文章编号】 1003—6350（2021）15—1909—06

Correlation between the expression levels of FGF2, CYSLTR1, RSAD2 and HLA-DRA and prognosis of diffuselarge B-cell lymphoma.
LIU Li, LI Shan-shan, YU Chu-ren, YUAN Yu, DAI Huai-jie, CAO Pei-jie. Department ofOncology and Hematology, Dongguan Houjie Hospital, Dongguan 523945, Guangdong, CHINA
【Abstract】 Objective To explore the correlation between the expression levels of immune related genesFGF2, CYSLTR1, RSAD2 and HLA-DRA and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods The ribonucleic acid (RNA) sequencing data of 221 and 48 DLBCL patients were obtained from the GeneExpression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, respectively. Univariate and multivariateCOX regression models and Kaplan-Meier curves were used to explore the correlation between the expression levels ofimmune-related genes and the overall survival (OS) of DLBCL patients. Moreover, the time-dependent receiver operat-ing characteristic curve (ROC) curve was used to evaluate the performance of risk stratification. Results The result ofthe univariate COX regression model indicated that the high expression of four immune-related genes FGF2, CYSLTR1,RSAD2 and HLA-DRA was significantly associated with poor OS of DLBCL patients [hazard ratio (HR)>1, P<0.05].The result was confirmed by Kaplan-Meier curves (P<0.05). Meanwhile, a multivariate COX regression model was fur-ther used to analyze the combination of FGF2, CYSLTR1, RSAD2 and HLA-DRA, which found that they can performrisk stratification of DLBCL patients, and that FGF2 contributed the greatest to the OS (coefficient β=0.27). Notably, uni-variate and multivariate COX regression analysis found that risk stratification was an independent prognostic factor forDLBCL patients. Furthermore, the time-dependent ROC curve showed that risk stratification had good performance [ar-ea under curve (AUC)>0.8]. Conclusion High expression of FGF2, CYSLTR1, RSAD2 and HLA-DRA was signifi-cantly associated with poor prognosis of DLBCL patients. Furthermore, the combination of these four immune-relatedgenes could perform risk stratification for DLBCL patients.
      【Key words】 Diffuse large B-cell lymphoma; Immune-related genes; Overall survival; Risk stratification; Bio-marker