STAT4在急性髓系白血病患者中的表达特征及其临床意义  

Expression and Clinical Significance of STAT4 in Acute Myeloid Leukemia

作　　者：焦一帆 王昊 刘宇辰 谷振阳 温亚男 王莉莉 窦立萍 Jiao Yifan;Wang Hao;Liu Yuchen(Department of Hematology,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100071,China)

机构地区：[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

出　　处：《华中科技大学学报（医学版）》2023年第6期781-790,共10页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：北京市自然科学基金资助项目(No.7222175);卫勤保障能力创新与生成专项(No.21WQ034);军委后勤保障部卫生局重点项目(No.21BJZ30)。

摘　　要：目的探索JAK/STAT(Janus kinase/signal transducer and activator of transcription)通路在急性髓系白血病(acute myeloid leukemia,AML)患者中的表达特征,分析其对患者生存预后的影响。方法在2个独立队列(n=64,n=121)中比较AML患者与健康人之间的差异表达基因,对这些基因进行通路富集;比较JAKs和STATs基因在AML患者与健康人中的表达水平;利用2个AML队列(n=163,n=403)基因表达数据、患者临床及预后信息,分析JAKs和STATs基因的临床价值。结果分析26例AML患者和38例健康人基因芯片表达结果,发现1266个具有显著表达差异基因(P_(adj)≤0.05,|log_(2)FC|≥0.5),其中有426个基因在AML患者中显著上调,840个基因在AML患者中显著下调,对这些基因进行通路富集,发现在AML患者中,JAK/STAT通路处于激活状态(P<0.05);对比GSE1159队列(n=121)中芯片数据,AML患者JAK1(P=0.019)、JAK2(P=0.047)和STAT4(P<0.01)基因表达水平高于健康人,STAT5A(P=0.028)和STAT6(P=0.022)基因表达水平低于健康人。单因素生存分析发现在TCGA与GSE68912个队列(n=163;n=403)中,STAT4高表达患者的总生存期(OS:P=0.02,HR=1.463;P=0.041,HR=1.293)和无事件生存期(EFS:P=0.01,HR=1.510)较STAT4低表达患者短。单因素和多因素COX分析证实,STAT4高表达是AML患者预后的独立危险因素(EFS:P=0.002,HR=1.958;OS:P=0.036,HR=1.556)。结论在急性髓系白血病患者中,JAK/STAT通路处于激活状态,STAT4表达量高于健康人群;STAT4基因表达上调提示预后不良,是AML患者预后的独立危险因素。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(P_(adj)≤0.05,|log_(2)FC|≥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 microarray data from the GSE1159 cohort(n=121)showed AML patients had higher levels of JAK1(P=0.019),JAK2(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 overall 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).Univariate 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 pathway 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 patien

关 键 词：急性髓系白血病 转录因子 STAT 预后 

分 类 号：R733.7[医药卫生—肿瘤]