[Expression and Prognostic Significance of B-cell Development-Related Genes in Children with Acute B Lymphoblastic Leukemia].

Abstract

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 1 097 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.