Expression and Clinical Significance of STAT4 in Acute Myeloid Leukemia
10.3870/j.issn.1672-0741.22.04.40
- VernacularTitle:STAT4在急性髓系白血病患者中的表达特征及其临床意义
- Author:
Yifan JIAO
1
;
Hao WANG
;
Yuchen LIU
Author Information
1. 中国人民解放军总医院第五医学中心血液病医学部,北京 100071
- Keywords:
acute myeloid leukemia;
transcription factor;
STAT;
prognosis
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2023;52(6):781-790
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the expression profile of the JAK/STAT pathway in patients with acute myeloid leukemia(AML)and to analyze its impact on the survival prognosis of patients.Methods This study compared differentially expressed genes between AML patients and healthy controls in 2 independent cohorts(n=64,n=121),and these genes were enriched by pathways.The expression levels of JAKs and STATs genes were compared between AML patients and healthy controls.The clinical values of JAK/STAT genes were analyzed using gene expression data,patients'clinical and prognostic information from 2 AML cohorts(n=163,n=403).Results Gene microarray expression results in 26 AML patients and 38 healthy controls showed 1266 genes with significantly differential expression(Padj≤0.05,| log2FC| ≥0.5),of which 426 genes were significantly upregulated in AML patients and 840 genes were significantly downregulated in AML patients.Pathway enrichment of these genes was performed in the JAK/STAT pathway,which was found to be active in AML patients(P＜0.05).Comparison of mi-croarray data from the GSE1159 cohort(n=121)showed AML patients had higher levels of JAK1(P=0.019),J AK2(P=0.047)and STAT4(P＜0.001)gene expression than the healthy controls,and their STAT5A(P=0.028)and STAT6(P=0.022)gene expression levels were lower than those in the healthy controls.Univariate survival analysis identified shorter over-all survival(P=0.02,HR=1.463;P=0.041,HR=1.293)and event-free survival(P=0.01,HR=1.510)in patients with high STAT4 expression than in those with a lower STAT4 expression in the TCGA and GSE6891 cohorts(n=163;n=403).Univa-riate and multifactorial COX analyzes confirmed that high STAT4 expression was an independent prognostic risk factor for AML patients(EFS:P=0.002,HR=1.958;OS:P=0.036,HR=1.556).Conclusion In AML patients,the JAK/STAT path-way is activated,and the STAT4 expression level is higher than that of the healthy controls.High expression of STAT4 suggest poor prognosis,wihich is an independent risk factor for the prognosis of AML patients.
