急性髓性白血病骨髓单个核细胞CPT1A表达与疗效的关系

Relationship between expression of CPT1A expression and therapeutic effect in bone marrow mononuclear cells of acute myeloidleukemia

目的检测急性髓性白血病患者骨髓单个核细胞中肉碱棕榈酰转移酶1a(CPT1A)表达与诱导化疗疗效和预后的关系。方法从GEO数据库收集GSE9476、GSE30029、GSE1159数据集中的患者基因表达谱资料,进行生物信息学分析。另收集2016年3月至2019年7月在我院初诊并接受诱导化疗的正常核型急性髓性白血病(CN-AML)86例。采用实时荧光定量PCR(qPCR)法检测骨髓单个核细胞中CPT1A表达。分析CPT1A表达与临床病理特征以及诱导化疗疗效的关系。Logistic回归分析影响疗效的因素,COX风险比例回归模型分析影响总生存时间(OS)的因素。结果GSE9476数据集中CPT1A在AML患者骨髓样本(5.18±0.94 vs.4.95±0.27,P<0.05)和外周血样本(5.23±1.33 vs.4.52±0.22,P<0.05)中高表达。GSE30029数据集中AML患者CD34+细胞中CPT1A表达高于健康献血者(6.51±1.20 vs.5.70±0.57,P<0.05)。qPCR结果显示,CN-AML患者骨髓单个核细胞中CPT1A相对表达量高于健康志愿者[1.25(1.03,1.73)vs.0.95(0.86,1.14),P<0.05]。多因素Logistic回归分析显示,CPT1A基因高表达是影响CN-AML患者诱导化疗疗效的独立危险因素(P<0.05)。CPT1A high组患者死亡率高于CPT1A low组中位OS短于CPT1A low组(18.0个月vs.未达),差异具有统计学意义(P<0.05)。多因素COX风险比例回归分析显示,CPT1A基因高表达是影响CN-AML患者OS的独立危险因素(P<0.05)。结论对于CN-AML患者,骨髓单个核细胞中CPT1A mRNA普遍升高,高表达的CPT1A mRNA是影响CN-AML患者化疗反应性和生存预后的独立危险因素。

Objective To investigate the expressions of carnitine palmityl transferase 1a(CPT1A)in bone marrow mononuclear cells of patients with acute myeloid leukemia and its relationship with chemotherapy response and adverse prognosis.Methods All clinical,cytogenetic and molecular information as well as microarray data of these patients in GSE9476,GSE30029 and GSE1159 data sets were all publicly downloaded at the Gene Expression Omnibus(GEO)and analyzed by bioinformatics.Another 86 cases of normal nuclear acute myeloid leukemia(CN-AML)were collected from March 2016 to July 2019.CPT1A expression in bone marrow mononuclear cells were detected by qPCR.All patient received the routine induction chemotherapy and were evaluated the response to treatment.The relationship between the expression of CPT1A and the clinicopathological characteristics and the efficacy of induced chemotherapy was analyzed.Logistic regression was used to analyze the factors affecting the efficacy,and Cox proportional risk regression model was used to analyze the factors affecting the overall survival time(OS).Results According to the GSE9476 dataset,CPT1A mRNA was highly expressed in bone marrow samples(5.18±0.94 vs.4.95±0.27,P<0.05)and peripheral blood samples(5.23±1.33 vs.4.52±0.22,P<0.05)of AML patients.According to GSE30029 Dataset,CPT1A mRNA expression in CD34+cells of AML patients was higher than that of healthy blood donors(6.51±1.20 vs.5.70±0.57,P<0.05).The relative expression of CPT1A mRNA in bone marrow mononuclear cells of CN-AML patients was higher than that of healthy volunteers by qPCR[1.25(1.03,1.73)vs.0.95(0.86,1.14),P<0.05].By multivariate Logistic regression analysis,CPT1A mRNA overexpression was an independent risk factor affecting the response of CN-AML patients to induction chemotherapy(P<0.05).The median OS was shorter than that in the CPT1A low Group(18.0 months vs.unreached)(P<0.05).Multivariate COX regression analysis showed that the overexpression of CPT1A mRNA was an independent risk factor for survival and prognosis in CN-AML patients(P<0.05).Conclusion CN-AML has high expression of CPT1A mRNA in bone marrow mononuclear cells,which would be an independent risk factor for chemotherapy responsiveness and survival in AML patients.