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中国循证儿科杂志

中国循证儿科杂志 ›› 2024, Vol. 19 ›› Issue (4): 281-286.DOI: 10.3969/j.issn.1673-5501.2024.04.004

• 论著 • 上一篇    下一篇

IDE基因表达水平在急性淋巴细胞白血病患儿中的预后意义

黄筱彤1a,史利欢2,薛天琳1a,梁静1a,李伟京1a,刘炜2,张瑞东1b,崔蕾1a,李志刚1   

  1. 1 国家儿童医学中心，首都医科大学附属北京儿童医院，儿科学国家重点学科，儿科重大疾病研究教育部重点实验室北京，100045；a 北京市儿科研究所血液疾病研究室，b 白血病科；2 郑州大学附属儿童医院，河南省儿童医院，郑州儿童医院，血液肿瘤科郑州，450018


  • 收稿日期:2024-07-17 修回日期:2024-10-16 出版日期:2024-08-25 发布日期:2024-10-31
  • 通讯作者: 李志刚，崔蕾

Prognostic significance of IDE gene expression levels in children with acute lymphoblastic leukemia

HUANG Xiaotong1a, SHI Lihuan2, XUE Tianlin1a, LIANG Jing1a, LI Weijing1a, LIU Wei2, ZHANG Ruidong1b, CUI Lei1a, LI Zhigang1   

  1. 1 National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China, a Hematologic Diseases Laboratory, Beijing Pediatric Research Institute, b  Leukemia Department; 2 Hematology and Oncology Department, Henan Children's Hospital, Zhengzhou Children's Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China
  • Received:2024-07-17 Revised:2024-10-16 Online:2024-08-25 Published:2024-10-31
  • Contact: LI Zhigang, email：ericlzg70@hotmail.com；CUI Lei，email：cuileilsh@163.com

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摘要： 背景：难治及复发的急性淋巴细胞白血病（ALL）患儿预后不良，寻找更多新的、具有预后价值的分子标志以协助判断预后具有重要意义。 目的：探讨ALL患儿中IDE基因表达水平及其与预后的相关性。 设计：回顾性队列研究。 方法：回顾性纳入首都医科大学附属北京儿童医院2020年1月1日至10月31日收治的ALL患儿作为测试队列，对患儿诊断时骨髓单个核细胞中的IDE基因表达水平行ROC曲线分析，并设定IDE界值，比较IDE高表达组和低表达组的预后差异；以河南省儿童医院2020年1月1日至10月31日收治的ALL患儿为验证队列，验证设定的IDE界值分组标准与预后的相关性。同时对临床生物学特征和早期治疗反应等行预后影响因素分析。 主要结局指标：无事件生存（EFS）。 结果：①本研究共纳入初治ALL患儿77例，测试队列37例，验证队列40例。②诊断时IDE基因表达水平与ALL预后相关，发生不良事件的患儿诊断时IDE基因表达水平显著高于无不良事件的患儿（P<0.001）。③ROC结果显示，IDE基因表达水平可预测ALL患儿的预后，AUC为0.961（P<0.001）。根据ROC曲线设定0.72为界值，测试队列中IDE高表达组（IDE≥0.72，n=19）的预后明显差于IDE低表达组（IDE＜0.72，n=18），3年EFS分别为55.7%和100%（P=0.002)。在验证队列中，IDE高表达组（n=26）和低表达组（n=14）的3年EFS分别为64.3%和96.2%（P=0.009)，差异有统计学意义。④多因素分析显示，临床危险度高危和IDE基因高表达是ALL患儿EFS独立预后因素，风险比分别为4.254（95%CI：1.080~17.554，P=0.039）和21.773（95%CI：2.632~180.125，P=0.004）。由这两个独立预后因素组成的复发风险指数的预测预后能力高于现行临床危险度分型（AUC分别为0.892和0.741，P=0.009）。 结论：IDE基因高表达与ALL患儿预后不良密切相关。

关键词: 急性淋巴细胞白血病, IDE, 基因表达, 预后

Abstract: Background：Children with refractory and relapsed acute lymphoblastic leukemia (ALL) have poor prognosis. It is significant to identify new molecular markers with prognostic value to assist in prognosis assessment. Objective：To explore the expression level of the IDE gene in children with ALL and its correlation with prognosis. Design：Retrospective cohort study. Methods：A total of 77 newly diagnosed ALL patients admitted to Beijing Children's Hospital, Capital Medical University, from January 1st, 2020, to October 31st, 2020, were included in the study as a testing cohort. The expression level of the IDE gene in bone marrow mononuclear cells at diagnosis was analyzed using ROC curve analysis to set the IDE cutoff value, comparing the prognosis of highexpression and lowexpression groups. The validation cohort consisted of ALL patients admitted to Henan Children's Hospital during the same period, and it was used to verify the correlation between the established IDE cutoff grouping criteria and prognosis. Prognostic factors, including clinical biological characteristics and early treatment responses, were also analyzed. Main outcome measures：Eventfree survival (EFS). Results：A total of 77 newly diagnosed ALL patients were included, with 37 in the testing cohort and 40 in the validation cohort. The expression level of the IDE gene at diagnosis was correlated with the prognosis of ALL. Patients with adverse events had significantly higher IDE expression levels at diagnosis than those without adverse events (P<0.001). ROC analysis showed that the IDE gene expression level could predict the prognosis of ALL patients, with an AUC of 0.961 (P<0.001). The cutoff value was set as 0.72 by the ROC curve. In the testing cohort, the highexpression group (IDE≥0.72, n=19) had a significantly worse prognosis than the lowexpression group (IDE<0.72, n=18), with 3year EFS rates of 55.7% and 100%, respectively (P=0.002). In the validation cohort, the highexpression group (n=26) and lowexpression group (n=14) had 3year EFS rates of 64.3% and 96.2% (P=0.009), which was statistically significant. Multivariate analysis indicated that high clinical risk and high IDE expression were independent prognostic factors for EFS in ALL patients, with risk ratios of 4.254 (95% CI: 1.08017.554, P=0.039) and 21.773 (95% CI: 2.632180.125, P=0.004), respectively. The predictive capacity of the recurrence risk index for prognosis, composed of these two independent prognostic factors, was higher than the current clinical risk stratification (AUCs of 0.892 and 0.741, P=0.009). Conclusion：High expression of the IDE gene is closely associated with poor prognosis in children with ALL.

Key words: Acute lymphoblastic leukemia, IDE, Gene expression, Prognosis