摘要
目的:分析代谢相关基因在儿童急性淋巴细胞白血病(ALL)中的表达及预后价值,探索新的预后判断标志物及治疗靶点。方法:以84例B细胞型ALL患儿作为研究对象,对所有样本转录组(RNA-Seq)测序数据中的代谢相关基因进行差异表达分析,利用COX单因素回归及Lasso回归方法构建代谢相关基因预后积分系统,COX多因素回归分析评价积分系统的预后价值,采用GSEA软件进行基因富集分析。结果:从转录组测序结果中共提取933个代谢相关基因的表达量数据进行差异表达分析,31个基因被鉴定为差异表达基因,其中14个基因在复发组表达上调,17个基因在复发组表达下调。进一步筛选出12个基因纳入预后积分系统,其中8个为复发组上调的基因(ASS1、CKM、PTGES、ADCY5、HNMT、PHGDH、CYP4F3、AADAT),4个为复发组下调的基因(GDA、DHRS9、IDO2、UGT2B4)。积分高风险组和低风险组的无复发生存率比较,差异具有统计学意义(P<0.05)。在纳入性别、年龄、初诊时白细胞计数、细胞及分子遗传学等临床特征后,该预后积分系统风险评分仍为疾病复发独立的危险因素(HR=8.906,95%CI:3.114-25.470)。GSEA结果显示,氨基糖和核苷酸糖代谢、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、乙醛酸和二羧酸代谢、嘧啶代谢、硒氨基酸代谢等通路在高风险组被显著富集。结论:代谢相关基因表达异常与儿童ALL预后相关,这些基因有望成为儿童ALL新的预后判断标志及治疗靶点。
Objective:To analyze the expression and prognostic value of metabolism-related genes in pediatric acute lymphoblastic leukemia(ALL),and explore the potential prognostic biomarkers or therapeutic targets.Methods:Transcriptome data from 84 children with B-cell ALL at the time of diagnosis and prior to any treatment were used to analyze the differential gene expression.A prognostic scoring system based on the expression of the metabolism-related genes was constructed using Cox and Lasso regression methods.The prognostic value of the scoring system was further assessed by multivariate Cox regression analysis.Gene set enrichment analysis was carried out by using GSEA software.Results:Among the 933 metabolism-related genes,14 up-regulated genes and 17 down-regulated genes were identified as differentially expressed genes.In addition,8 up-regulated genes(ASS],CKM,PTGES,ADCY5,HNMT,PHGDH,CYP4 F3,AADAT)and 4 down-regulated genes(CDA,DHRS9,ID02,UGT2 B4)were selected to establish a novel prognostic scoring system.Patients in the high-risk group showed poorer survival significantly than patients in the low-risk group(P<0.05).The prognostic scoring system was still shown to be an independent prognostic factor for the survival of children with ALL after the clinical characteristics,such as gender,age,white blood cell count at initial diagnosis,cytogenetics and molecular genetics were included(HR=8.906,95%CI:3.114-25.470).GSEA results showed that 6 metabolism-related pathways(amino sugar and nucleotide sugar metabolism,arginine and proline metabolism,fructose and mannose metabolism,glyoxylate and dicarboxylate metabolism,pyrimidine metabolism,selenoamino acid metabolism)were enriched in the high-risk group.Conclusion:The abnormal metabolism-related gene expression is associated with the clinical outcome of children with ALL,and these results provide potential novel prognostic biomarkers and treatment targets for pediatric ALL.
作者
张豪
成娟
马海珍
赵龙
席亚明
ZHANG Hao;CHENG Juan;MA Hai-Zhen;ZHAO Long;XI Ya-Ming(Department of Hematology,The First Hospital of Lanzhou University,Lanzhou 730000,Gansu Province,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2021年第5期1375-1379,共5页
Journal of Experimental Hematology
关键词
代谢
儿童
急性淋巴细胞白血病
预后
metabolism
pediatric
acute lymphoblastic leukemia
prognosis
