血糖及糖代谢基因对急性髓细胞性白血病预后的意义

Significance of blood glucose levels and glucose metabolism-related genes on the prognosis of acute myeloid leukemia

摘要:

目的 探讨血糖水平与急性髓细胞性白血病（AML）患者疾病状态、危险分层及基因突变等之间的相关性，分析糖代谢相关基因在AML预后中的意义。方法 选取2017年4月至2021年5月在中南大学湘雅医院血液科就诊的280例AML初诊患者作为研究样本。收集患者在不同疾病阶段（初诊、缓解和复发）治疗前的血糖水平数据，并采用t检验或方差分析进行组间对比。通过Cox回归分析筛选与AML预后相关的糖代谢基因，并借助时间受试者操作特征（ROC）曲线进一步筛选具有良好预测性能的基因。根据预后基因表达水平将AML患者分为高表达组和低表达组，并绘制Kaplan-Meier生存曲线。结果 AML患者在初治和复发组的血糖水平高于缓解组（P<0.05）。根据2022版欧洲白血病网（ELN）指南进行预后危险分层，结果显示高危组患者的血糖水平高于低、中危组（P=0.046）。此外，NPM1突变组的血糖水平高于非突变组（P=0.035），而年龄、法美英（FAB）分型、染色体核型、FLT3基因突变、CEBPA基因突变与血糖水平之间差异无统计学意义（P>0.05）。根据Cox回归分析和时间ROC曲线筛选出6个与AML预后相关且预测效能较好的糖代谢相关基因（P<0.05），分别为PLA2G4A、PTPN1、SORT1、CTH、AKAP9和MLYCD，其中前3个基因高表达使AML患者总体生存率显著下降（P<0.05），而后3个基因高表达则显著提高患者总体生存率（P<0.05）。结论 血糖水平与AML患者疾病状态、危险分层及NPM1基因突变相关；基于糖代谢相关基因预后风险分析可用于预测AML患者总生存率。

Abstract:

Objective To investigate the correlation between blood glucose levels and the disease status, risk stratification and gene mutations of patients with acute myeloid leukemia (AML) and analyze the significance of glucose metabolism-related genes in AML prognosis.Methods This study included 280 newly diagnosed AML patients admitted to the Hematology Department of Xiangya Hospital from April 2017 to May 2021. Blood glucose level data before treatment were collected from patients in different disease stages (initial diagnosis, remission, and relapse), and t-tests or analysis of variance for inter-group comparisons was utilized. Cox analysis was used to screen glucose metabolism-related genes associated with AML prognosis, and followed by leveraging time receiver operating characteristic (ROC) curves for further selection of genes with excellent predictive performance. Based on prognostic gene expression levels, patients were divided into high-expression and low-expression groups. Subsequently, Kaplan-Meier survival curves were plotted to assess the prognostic value of those genes.Results The blood glucose levels in AML patients were notably higher in the newly diagnosed and relapsed groups compared with the remission group (P<0.05). Patients were classified into low, intermediate and high-risk group based on the 2022 version of the European LeukemiaNet (ELN) guidelines, and the blood glucose levels of high-risk patients were higher than those in the low and intermediate-risk groups (P=0.046). Furthermore, blood glucose levels were higher in NPM1-mutated group (P=0.035); however, there was no statistically significant difference of blood glucose levels among different age, FAB classification, cytogenetics, FLT3 mutation, and CEBPA mutation (P>0.05). Six glucose metabolism-related genes significantly associated with AML prognosis were identified using Cox regression analysis and time ROC curve (P<0.05). These genes included PLA2G4A, PTPN1, SORT1, CTH, AKAP9, and MLYCD, among which the high expression of the first three genes remarkably decreased overall survival rate in AML patients (P<0.05), while elevated expression of the latter three genes significantly improved patient overall survival rate (P<0.05).Conclusion The blood glucose levels were associated with the disease status, risk stratification and NPM1 mutation in AML patients. And the prognostic risk analysis based on glucose metabolism-related genes can predict the overall survival of AML patients.