河北医科大学学报 ›› 2022, Vol. 43 ›› Issue (12): 1390-1396,1438.doi: 10.3969/j.issn.1007-3205.2022.12.005

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VNN1基因在急性髓系白血病中的表达及临床意义

  

  1. 武汉大学中南医院血液内科,湖北 武汉 430000

  • 出版日期:2022-12-25 发布日期:2023-01-11
  • 作者简介:吴八路(1985-),男,湖北武汉人,武汉大学中南医院主治医师,医学硕士,从事血液系统恶性疾病的发病机制与临床研究。

The expression and clinical significance of VNN1 in acute myeloid leukemia

  1. Department of Hematology, Zhongnan Hospital of Wuhan University, Wubei Province, Wuhan 430000, China
  • Online:2022-12-25 Published:2023-01-11

摘要: 目的 通过在线数据库挖掘分析VNN1基因在急性髓性白血病(acute myeloid leukemia,AML)中的表达并探讨其临床意义。
方法 使用癌症基因图谱(the cancer genome atlas,TCGA)、组织特异性基因表达库(the genotype-tissue expression,GTEx)和高通量基因表达数据集(gene expression omnibus,GEO)等数据库分析VNN1基因在AML患者和正常对照组中的表达水平; 通过下载TCGA、GEO数据集中AML患者的数据信息,进行VNN1基因表达水平与临床特征及总体生存期的相关性分析; 利用STRING数据库分析VNN1蛋白-蛋白互作网络,并进行GO基因富集和KEGG通路富集分析,通过单样本基因集富集分析(ssGSEA)来评估VNN1与免疫细胞浸润之间的相关性。
结果 与健康对照组(0.025±0.053)相比,VNN1在AML中显著高表达(3.306±1.991)(P<0.001),且其表达水平与AML患者细胞遗传学风险、FLT3突变状态、NPM1突变状态存在密切关系(P<0.05);ROC曲线表明VNN1的表达水平可以准确区分正常人群和AML患者(曲线下面积为0.969);生存分析结果显示VNN1低表达的AML患者中位生存期为27.4个月,而高表达组中位生存期只有10.1个月,差异有统计学意义( P<0.001) 。单因素和多因素COX回归分析均表明高表达的VNN1是AML总体预后的独立危险因素(风险比分别为1.998,1.763)(P<0.05);STRING数据库显示与VNN1相互作用的蛋白有PANK1、PANK3、PANK2、VNN2、VNN3、SERPIN2、TAAR2、TAAR5、TAAR1、STX7。GO功能及KEGG信路通路的富集分析显示VNN1主要参与的生物学过程包括囊泡运输中的核心蛋白复合体相互作用、泛酸和辅酶A生物合成、补体和凝血级联反应过程、血小板活化等。
结论 通过对在线数据库进行挖掘分析发现,VNN1在AML中显著高表达且与患者总体生存期呈负相关,为进一步深入研究AML发病机制和靶向治疗提供了理论依据。


关键词: 急性髓系白血病, 预后标志, 免疫浸润

Abstract: Objective To analyze the expression and clinical significance of VNN1 gene in acute myeloid leukemia(AML) through online database mining. 
Methods In this study, we analyzed the expression level of VNN1 gene in AML patients and normal control groups based on the cancer genome atlas (TCGA), the genotype-tissue expression (GTEx), and gene expression omnibus (GEO) databases. The correlation of VNN1 gene expression level with clinical characteristics and overall survival was analyzed with TCGA and GEO datasets by downloading the data information of AML patients. The STRING database was used to analyze VNN1 protein-protein interaction (PPI)network, and GO gene enrichment and KEGG pathway enrichment were analyzed. The correlation between VNN1 and immune cell infiltration was evaluated by single-sample gene set enrichment analysis (ssGSEA). 
Results Compared with healthy controls (0.025±0.053), VNN1 was significantly highly expressed in AML (3.306±1.991) (P<0.001), and its expression level was closely associated with AML patients′ cytogenetic risk, FLT3 mutation status, and NPM1 mutation (P<0.05). The receiver operating characteristic (ROC) curve showed that the expression level of VNN1 could accurately distinguish the normal population and AML patients (AUC=0.969). The K-M curve showed that the median survival time of AML patients with low VNN1 expression was 27.4 months, which, however,was only 10.1 months in the high expression group, suggesting significant differences (P<0.001). Univariate and multivariate COX regression analyses showed that high expression of VNN1 was an independent risk factor for the overall prognosis of AML (HR=1.998, 1.763) (P<0.05). STRING database showed that the proteins interacting with VNN1 included PANK1, PANK3, PANK2, VNN2, VNN3, SERPIN2, TAAR2, TAAR5, TAAR1 and STX7. The enrichment analysis of GO function and KEGG pathway showed that VNN1 mainly participated in biological processes including SNARE interactions in vesicular transport, pantothenate and CoA biosynthesis, complement and coagulation cascades, and platelet activation. 
Conclusion Through the analysis of online databases, NN1 is significantly highly expressed in AML and negatively correlated with the overall survival of patients, which provides a theoretical basis for further in-depth study of the pathogenesis and targeted treatment of AML.


Key words: acute myeloid leukemia, biomarker, immune cell infiltration