B细胞发育相关基因在儿童急性B淋巴细胞白血病中的表达及预后意义  

Expression and Prognostic Significance of B-cell Development-Related Genesin Children with Acute B Lymphoblastic Leukemia

作　　者：尹莎 刘安生[2] 樊晔 夏蕊 张艳敏[1] YIN Sha;LIU An-Sheng;FAN Ye;XIA Rui;ZHANG Yan-Min(Shaanxi Institute for Pediatric Diseases,Shaanxi Provincial Key Laboratory of Children’s Health and Diseases,Xi’an Children’s Hospital;Department of Hematological Oncology,Xi’an Children’s Hospital,Xi’an 710003,Shaanxi Province,China)

机构地区：[1]西安市儿童医院陕西省儿科疾病研究所,陕西省儿童疾病精准医学重点实验室 [2]西安市儿童医院血液肿瘤科,陕西西安710003

出　　处：《中国实验血液学杂志》2024年第6期1665-1675,共11页Journal of Experimental Hematology

基　　金：陕西省自然科学基础研究计划(2022JQ-781);西安市儿童医院科研项目(2021B01)。

摘　　要：目的:分析B细胞发育相关基因在儿童急性B淋巴细胞白血病(B-ALL)中的表达,探索B细胞发育相关基因与B-ALL患儿预后的相关性。方法:基于GEO和TARGET数据库,分析健康对照者与B-ALL患儿差异表达的B细胞发育相关基因及其在B-ALL复发组和未复发组的差异表达。采用Cox单因素回归及Lasso回归方法筛选候选基因并构建B-ALL特异性的B细胞发育相关基因的预后模型。通过Cox多因素回归评估所构建的预后模型的应用价值,并分析B-ALL不同亚型的风险评分情况。在真实世界中,通过B-ALL患儿转录组测序结果验证B细胞发育相关基因预后模型与临床结局之间的相关性。此外,还分析了该预后模型与其他B-ALL预后模型的相关性。最后,采用Metascape评估与该预后模型相关基因的信号通路及功能富集状态,以探究其潜在机制。结果:在B-ALL中特异性表达且与B细胞发育相关的基因共1097个,其中27个基因在B-ALL复发组中表达上调,37个基因在B-ALL复发组中表达下调。采用Cox单因素回归及Lasso回归方法,筛选出14个基因纳入B细胞发育相关基因的预后模型(CDC25B、CKAP4、DSTN、IGF2R、NDUFA4、ODC1、PAX5、SH3BP4、SLC27A5、APAF1、ARRB2、HHEX、IL13RA1、UVRAG)。基于14个基因的预后模型对TARGET数据库中134例B-ALL患儿进行风险评分,高风险评分组(评分>0.11)的患儿预后差于低风险评分组(评分≤0.11)的患儿。Cox多因素分析显示,该B细胞发育相关基因的风险评分可作为B-ALL患儿独立预后因素,并且低风险评分组中高二倍体阳性患儿的比例显著高于高风险评分组,而高风险评分组中TCF3/PBX1阳性患儿的比例显著高于低风险评分组。同时,真实世界数据显示,高风险评分组的B-ALL患儿预后差于低风险评分组的患儿,且B-ALL死亡组患儿B细胞发育相关基因的风险评分高于B-ALL未死亡组。此外,根据代谢相关基因预后积分系统计算的风险评分�Objective:To analyze the expression of B-cell development-related genes in acute B lymphoblastic leukemia(B-ALL),and to explore the relationship between B-cell development-related genes and the prognosis of B-ALL patients.Methods:The GEO and TARGET databases were integrated to analyze the differential expression of B-cell development-related genes between the healthy persons and B-ALL patients and their differential expression in the B-ALL relapse and non-relapse groups.Cox single factor regression and Lasso regression were used to constructe a B-ALL specific prognosis model of B-cell development-related genes.The prognostic value of this model was analyzed by Cox multiple factor regression.The risk scores of different subtypes of B-ALL was analyzed.In the real world,the correlation between the prognostic model of B-cell development-related genes and clinical outcomes was verified through the transcriptome sequencing results of B-ALL patients.In addition,the correlation between this prognostic model and other B-ALL prognostic models was also analyzed.At last,Metascape was used to evaluate the pathway and function enrichment status related to the prognosis model.Results:There were 1097 genes specifically expressed in B-ALL and related to B cell development,27 of which were up-regulated in the B-ALL relapse group,and 37 genes were down-regulated in the B-ALL relapse group.14 genes were further selected to be included in the B-cell development-related prognosis model(CDC25B,CKAP4,DSTN,IGF2R,NDUFA4,ODC1,PAX5,SH3BP4,SLC27A5,APAF1,ARRB2,HHEX,IL13RA1,UVRAG)based on Cox single factor regression and Lasso regression.Risk scoring of patients with B-ALL based on the 14 genes prognosis model,the prognosis of 134 patients in the low-risk scoring group(score>0.11)was better than those in the patients with high-risk scores(score≤0.11).Multivariate analysis showed that the risk score of B-cell development-related genes was an independent prognostic factor.And the proportion of hyperdiploid positive children in the low-risk sco

关 键 词：B细胞发育相关基因 急性B淋巴细胞白血病 预后 儿童 

分 类 号：R733.7[医药卫生—肿瘤]