脂肪酸代谢相关基因ACSL1在急性髓系白血病中的作用及潜在价值

Involvement of the fatty acid metabolism-related gene ACSL1 in acute myeloid leukemia

目的:通过生物信息学数据分析脂肪酸代谢相关基因长链酯酰辅酶A合成酶1(ACSL1)在急性髓系白血病(AML)中的作用及潜在价值。方法:使用基因表达谱交互分析(GEPIA)数据库分析ACSL1基因在AML患者和健康对照人群中的表达水平。使用R包(以最优截断值10.73为高、低表达的分界)survminer绘制ACSL1高、低表达组的Kaplan-Meier生存曲线,分析ACSL1基因表达与AML患者生存率之间的相关性。使用R语言中timeROC包绘制ACSL1的受试者工作特征(ROC)曲线,探究ACSL1基因对正常和AML患者的诊断效率。通过单基因富集分析(GSEA),明确ACSL1基因的作用通路。采用Kaplan-Meier生存分析确定ACSL1表达水平与患者总生存期(OS)之间的关系。通过单因素和多因素Cox回归分析建立预后模型,确定ACSL1是否为AML的独立预后因素以及验证模型的预测效果。结果:ACSL1在AML患者中的表达水平较健康对照组明显升高(P<0.05),对AML具有诊断意义,且ACSL1高表达组患者生存较差,预后不良(P=0.045)。ROC曲线显示,ACSL1诊断AML患者1、2、3年生存时间的曲线下面积(AUC)均大于0.6,说明ACSL1预测准确率较高。富集分析表明,ACSL1主要通过脂肪酸降解、脂肪酸代谢等途径在AML发生和发展中发挥重要作用。单因素Cox分析显示年龄和ACSL1表达水平是影响AML患者总生存率的高风险因素(HR>1,P<0.05),多因素Cox分析显示年龄、染色体异常分数、基因突变分数是AML影响患者预后的独立因素(P<0.05)。结论:脂肪酸代谢相关基因ACSL1在AML中高表达,在多个致癌通路和脂肪酸代谢通路中富集,与不良预后密切相关,可作为AML的潜在治疗靶点和预后生物标志物。

OBJECTIVE:To analyze involvement of the fatty acid metabolism-related gene,long-chain esteryl-CoA synthetase 1(ACSL1),in acute myeloid leukemia(AML)through bioinformatics analysis.METHODS:Expression levels of the ACSL1 gene in AML patients and healthy controls were analyzed using the Gene Expression Profiling Interaction Analysis(GEPIA)database.The Kaplan-Meier survival curves for the ACSL1 high and low expression groups were plotted by using R-package survminer,and correlations between the ACSL1 gene expression and the survival rate of AML patients were analyzed.The receiver operating characteristic(ROC)curve of ACSL1 was plotted using the timeROC package in R language to explore the diagnostic efficiency of ACSL1 gene in controls and AML patients.Single gene enrichment analysis(GSEA)was used to clarify the oncogenic and lipid metabolism pathways of ACSL1 gene.Kaplan-Meier survival analysis was used to determine relationships between ACSL1 expression level and overall survival(OS).Univariate and multivariate Cox regression analysis were used to establish a prognostic model and to determine whether ACSL1 was an independent prognostic factor for AML,and to investigate the prediction effect of the model.RESULTS:The expression levels of ACSL1 in AML patients were significantly higher than those in the controls(P<0.05),and they had high diagnostic significance for the AML patients.In addition,patients in the ACSL1 high expression group had poor survival and poor prognosis(P=0.045).The ROC curve showed that the area under the curve(AUC)of ACSL1 in diagnosing the 1-,2-,and 3-year survival time of AML patients was greater than 0.6,indicating that the prediction accuracy of ACSL1 was high.Enrichment analysis showed that ACSL1 played an important role in the occurrence and development of AML,mainly through fatty acid degradation and metabolism.Univariate Cox analysis showed that age and ACSL1 expression level were high-risk factors affecting the overall survival rate of AML patients(HR>1,P<0.05),and multivariate Cox analysis showed that age,chromosomal abnormality score and gene mutation score were independent factors affecting the prognosis of AML patients(P<0.05).CONCLUSION:ACSL1,a fatty acid metabolism-related gene,is highly expressed in AML,and enriched in multiple oncogenic and fatty acid metabolism pathways.Its high expression was closely related to poor prognosis and,therefore,the expression can be used as a potential therapeutic target and prognostic biomarker for AML.