Expression and Prognostic Significance of B-cell Development-Related Genes in Children with Acute B Lymphoblastic Leukemia
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 scoring group was significantly higher than that in the high-risk scoring group,while the proportion of TCF3/PBX1 positive children in the high-risk scoring group was significantly higher than that in the low-risk scoring group.At the same time,the real-world data showed that the prognosis of patients with B-ALL in the high-risk scoring group was worse than those of the patients with low-risk scores in Xi'an Children's Hospital.And the risk score of B-cell development-related genes in patients with B-ALL death was higher than that in patients with B-ALL non-death.In addition,there is a positive correlation between the risk score calculated by the metabolic-related gene prognostic scoring system and the risk score calculated by the B-cell developmental-related gene prognostic model.At last,differential gene enrichment analysis suggested that the prognosis risk was related to the process of embryonic development and differentiation to various systems,especially to the B cell receptor signaling pathway.Conclusion:The specific expression of B-cell development-related genes in B-ALL is related to the prognosis of B-ALL.The prognosis model composed of 14 genes is expected to be a new prognostic marker for children with B-ALL.
B-cell development-related genesacute B lymphoblastic leukemiaprognosischildren
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维普
