Construction of m6A modification related prognostic model in older patients with FLT3 mutated acute myeloid leukemia
10.3760/cma.j.issn.0254-9026.2024.03.015
- VernacularTitle:基于m6A修饰相关基因构建FLT3突变型老年急性髓系白血病患者预后模型
- Author:
Luyao LONG
1
;
Jie GUO
;
Simei REN
Author Information
1. 北京医院 国家老年医学中心 国家卫生健康委临床检验中心 中国医学科学院老年医学研究院，北京 100730
- Keywords:
Leukemia, myeloid, acute;
DNA mutational analysis;
Genes;
Prognosis
- From:
Chinese Journal of Geriatrics
2024;43(3):354-360
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen m6A modification-related genes, and to establish a prognostic model in patients with FLT3 mutated acute myeloid leukemia(AML), especially in older patients and to evaluate the prognostic efficiency of the model.Methods:Gene expression omnibus(GEO)datasets were used to analyze abnormally expressed m6A enzymes and reading proteins in FLT3 mutated AML; Correlation analysis was used to screen m6A modified-related genes in expression profiles.By integrating TCGA and BEAT data, 83 FLT3 mutated AML patients were included, and 32 of them were older than 60 years.Univariate Cox analysis and Lasso regression were conducted to construct the risk model.Kaplan-Meier curve and time-dependent receiver operating characteristic curve(tROC)were used to evaluate the prognostic efficiency of the model; subgroup analysis was conducted in the older patients.The concordance index(C-index)and calibration curve were used to evaluate the discrimination and accuracy of the model.Results:14 m6A modification enzymes or reading proteins were abnormally expressed in patients with FLT3 mutated AML.Correlation analysis filtered out 2 476 m6A related genes in expression profile.In TCGA and BEAT integrated data, univariate Cox analysis identified 132 prognostic genes.Lasso regression selected seven candidate genes to establish the prognostic risk model, including AKAP9, AVEN, DMCA1, DPYD, FAR2, GPHN and SPECC1L.Kaplan-Meier curve showed that high-risk group of the model had significantly shorter overall survival with a hazard ratio( HR)of 5.08(95% CI: 2.54-10.14, P<0.001).The area under the curve(AUC)in tROC for 1-year survival was 0.83; the C-index of risk model was 0.737.In older patients, the hazard ratio( HR)of the risk model for 1-year overall survival was 3.40(95% CI: 1.25-9.24, P=0.017)with an AUC of 0.79. Conclusions:The risk model based on m6A modified-related genes has some predictive value in assessing the prognosis of patients with FLT3 mutated AML, especially indicative to prognosis prediction in the elderly.
