YTHDF2基因在急性髓细胞白血病中的生物信息学研究  

Bioinformatics study of YTHDF2 gene in acute myeloid leukemia

作　　者：周仁龙 张勇刚 黄国清 周平 唐丹丹 Zhou Renlong;Zhang Yonggang;Huang Guoqing;Zhou Ping;Tang Dandan(Department of Blood Transfusion,Longhua District Central Hospital,Shenzhen 518100,Guangdong Province,China;Department of Clinical Laboratory,Longhua District Central Hospital,Shenzhen 518100,Guangdong Province,China;Headquarters of Shenzhen Nanshan Medical Group,Shenzhen 518000,Guangdong Province,China)

机构地区：[1]深圳市龙华区中心医院输血科,深圳518100 [2]深圳市龙华区中心医院检验科,深圳518100 [3]深圳市南山区医疗集团总部,深圳518000

出　　处：《国际输血及血液学杂志》2024年第5期411-421,共11页International Journal of Blood Transfusion and Hematology

基　　金：广东省自然科学基金面上项目(2022A1515012542)。

摘　　要：目的基于生物信息学方法研究m^(6)A RNA结合蛋白(YTHD)F2基因在急性髓细胞白血病(AML)中的表达及临床意义。方法从UCSC Xena数据库癌症基因组图谱(TCGA)Pan-Cancer(PANCAN)数据集中提取YTHDF2 mRNA在泛癌(34种癌症样本,N=10535,G=60499)和AML患者(n=173)中的表达数据。使用SangerBox生物医学数据分析盒分析YTHDF2 mRNA在泛癌肿瘤组织及其对应正常组织样本,在AML组织及其配对正常外周血样本中的表达差异,以及YTHDF2 mRNA表达与RNA修饰标记基因和免疫细胞浸润水平的关系。使用UALCAN数据库分析TCGA-AML数据集(n=171)中YTHDF2 mRNA在不同AML亚型中的表达差异。利用STRING数据库进行AML中YTHDF2的蛋白互作网络分析。使用R软件进行YTHDF2基因的京都基因与基因组百科全书(KEGG)信号通路富集分析和基因本体(GO)功能注释分析。不同特征样本中YTHDF2 mRNA表达量的比较,采用Wilcoxon符号秩和检验或Kruskal-Wallis H检验。YTHDF2 mRNA表达量与免疫细胞浸润水平、RNA修饰标记基因的关系使用Pearson或Spearman相关性分析法。采用Kaplan-Meier法绘制不同特征AML患者的生存曲线,其总体生存(OS)率的比较采用Log-rank检验。结果①YTHDF2 mRNA表达量在胃癌、结肠癌、头颈鳞状细胞癌等29种癌症的肿瘤组织样本中较正常组织样本显著升高(均为P<0.05),在肾嫌色细胞癌、肾乳头状细胞癌、肾上腺皮质癌的肿瘤组织样本中显著降低(均为P<0.05)。②AML组织样本的YTHDF2 mRNA表达量较其配对外周血样本显著升高,差异有统计学意义[5.75 TPM(5.46,5.96 TPM)比2.60 TPM(1.56,3.34 TPM),Z=24.66,P<0.001]。不同亚型AML患者的YTHDF2 mRNA表达量比较,差异有统计学意义(H=12.45,P=0.03),其中表达量居前两位的亚型为AML-M6、M7。③YTHDF2 mRNA高表达患者(n=42)的OS率较YTHDF2 mRNA低表达者(n=100)显著降低,并且差异有统计学意义(χ^(2)=18.11,P<0.001)。④AML中YTHDF2 mRNA表达与44种RNA修饰标记基因ObjectiveTo investigate the expression and clinical significance of m^(6)A RNA-binding protein(YTHD)F2 gene in acute myeloid leukemia(AML)based on bioinformatics methods.MethodsThe expression data of YTHDF2 mRNA in pan-cancer(including 34 types of cancer,N=10535,G=60499)and AML patients(n=173)were extracted from the Cancer Genome Atlas(TCGA)Pan-Cancer(PANCAN)dataset in UCSC Xena database.The SangerBox biomedical data analysis box was used to analyze the expression differences of YTHDF2 mRNA between tumor tissues and corresponding normal tissue samples in pan-cancer,and between AML tissues and paired normal peripheral blood samples,as well as to analyze the relationship between YTHDF2 mRNA expression and RNA modification marker genes and immune cell infiltration levels.The UALCAN database was used to analyze the expression differences of YTHDF2 mRNA among different AML subtypes in the TCGA-AML dataset(n=171).The STRING database was used to analyze the protein interaction network of YTHDF2.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis and gene ontology(GO)functional annotation analysis of the YTHDF2 gene were performed using R software.The Wilcoxon signed rank test or Kruskal-Wallis H test was used to compare the expression of YTHDF2 mRNA in samples with different characteristics.The Pearson or Spearman correlation analysis method was used to analyze the relationships between the expression of YTHDF2 mRNA and the infiltration level of immune cell and RNA modification marker genes.The Kaplan-Meier method was used to draw the survival curves of AML patients with different characteristics,and the overall survival(OS)rates were compared using the Log-rank test.Results①Compared with normal tissue samples,the expression of YTHDF2 mRNA was significantly increased in tumor tissue samples of 29 types of cancer,including gastric cancer,colon cancer,head and neck squamous cell carcinoma(all P<0.05),and significantly decreased in tumor tissue samples of renal chromophobe cell carcinoma,re

关 键 词：白血病 髓样 急性 YTHDF2蛋白 人类 RNA甲基化 蛋白质相互作用图 基因本体 m^(6)A 生物信息学 

分 类 号：R733.71[医药卫生—肿瘤]