Development and validation of a promising 5-gene prognostic model for pediatric acute myeloid leukemia

作者全名："Tao, Yu; Wei, Li; Shiba, Norio; Tomizawa, Daisuke; Hayashi, Yasuhide; Ogawa, Seishi; Chen, Li; You, Hua"

作者地址："[Tao, Yu; You, Hua] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,Dept Pedia, Minist Educ,Key Lab Child Dev & Disorders,China In, Chongqing, Peoples R China; [Wei, Li] Chongqing Populat & Family Planning Sci & Technol, NHC Key Lab Birth Defects & Reprod Hlth, Chongqing, Peoples R China; [Wei, Li] Chongqing Hosp Tradit Chinese Med, Chongqing, Peoples R China; [Shiba, Norio] Yokohama City Univ, Grad Sch Med, Dept Pediat, Yokohama, Japan; [Tomizawa, Daisuke] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Div Leukemia & Lymphoma, Tokyo, Japan; [Hayashi, Yasuhide] Jobu Univ, Gunma & Inst Physiol & Med, Gunma Childrens Med Ctr, Dept Hematol Oncol, Isesaki, Gunma, Japan; [Ogawa, Seishi] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan; [Ogawa, Seishi] Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Kyoto, Japan; [Ogawa, Seishi] Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, S-17177 Stockholm, Sweden; [Chen, Li] Fudan Univ, Sch Basic Med Sci, Dept Cellular & Genet Med, Shanghai 200032, Peoples R China"

通信作者："You, H (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Pediat,Childrens Hosp,Dept Pedia, Minist Educ,Key Lab Child Dev & Disorders,China In, Chongqing, Peoples R China."

来源：MOLECULAR BIOMEDICINE

ESI学科分类：　

WOS号：WOS:001132326700001

JCR分区：Q3

影响因子：4

年份：2024

卷号：5

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Pediatric acute myeloid leukemia; Risk stratification; Prognostic; C-index

摘要："Risk classification in pediatric acute myeloid leukemia (P-AML) is crucial for personalizing treatments. Thus, we aimed to establish a risk-stratification tool for P-AML patients and eventually guide individual treatment. A total of 256 P-AML patients with accredited mRNA-seq data from the TARGET database were divided into training and internal validation datasets. A gene-expression-based prognostic score was constructed for overall survival (OS), by using univariate Cox analysis, LASSO regression analysis, Kaplan-Meier (K-M) survival, and multivariate Cox analysis. A P-AML-5G prognostic score bioinformatically derived from expression levels of 5 genes (ZNF775, RNFT1, CRNDE, COL23A1, and TTC38), clustered P-AML patients in training dataset into high-risk group (above optimal cut-off) with shorter OS, and low-risk group (below optimal cut-off) with longer OS (p < 0.0001). Meanwhile, similar results were obtained in internal validation dataset (p = 0.005), combination dataset (p < 0.001), two treatment sub-groups (p < 0.05), intermediate-risk group defined with the Children's Oncology Group (COG) (p < 0.05) and an external Japanese P-AML dataset (p = 0.005). The model was further validated in the COG study AAML1031(p = 0.001), and based on transcriptomic analysis of 943 pediatric patients and 70 normal bone marrow samples from this dataset, two genes in the model demonstrated significant differential expression between the groups [all log2(foldchange) > 3, p < 0.001]. Independent of other prognostic factors, the P-AML-5G groups presented the highest concordance-index values in training dataset, chemo-therapy only treatment subgroups of the training and internal validation datasets, and whole genome-sequencing subgroup of the combined dataset, outperforming two Children's Oncology Group (COG) risk stratification systems, 2022 European LeukemiaNet (ELN) risk classification tool and two leukemic stem cell expression-based models. The 5-gene prognostic model generated by a single assay can further refine the current COG risk stratification system that relies on numerous tests and may have the potential for the risk judgment and identification of the high-risk pediatric AML patients receiving chemo-therapy only treatment."

基金机构：National Natural Science Foundation of China

基金资助正文：The authors thank all participants and recruiting centers of all the included studies.