摘要
目的分析代谢异常型肥胖(metabolically unhealthy obesity,MUO)和代谢正常型肥胖(metabolically healthy obesity,MHO)儿童的全血转录组特征,探讨MUO的生物标志物。方法采用Gene Expression Omnibus(GEO)数据库的GSE146869数据集,包括27例肥胖儿童的全血转录组测序数据,其中13例MHO儿童,14例MUO儿童。利用R软件的“Limma”包,分析全血细胞中的差异表达基因。使用基因本体论(gene ontology,GO)富集分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析、蛋白互作(protein-protein interaction,PPI)网络分析等生物信息学方法,探索差异表达基因的生物学功能。使用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA),将差异表达基因聚类为模块,探索MUO的生物标志物或潜在治疗靶点。使用R软件进行生物信息分析和统计学分析。结果MHO组与MUO组儿童的性别、年龄、体质量指数、收缩压、舒张压、空腹血糖、胰岛素含量和胰岛素抵抗指数比较,差异均无统计学意义(P值均>0.05)。MUO组血清三酰甘油、白细胞介素-6和肿瘤坏死因子-α含量高于MHO组(P值均<0.05)。与MHO组相比,MUO组上调109个基因,下调77个基因。186个差异表达基因富集到46个GO条目和3条KEGG通路。其中,细胞分裂周期5样蛋白(cell division cycle 5 like,CDC5L)、CTP合酶1(CTP synthase 1,CTPS1)和主要组织相容性复合体ⅠC(major histocompatibility complex classⅠ-C,HLA-C)基因为PPI网络图的枢纽基因。WGCNA将186个差异表达基因聚类生成5个模块,在青色模块中,切割和聚腺苷酸化特异因子7(cleavage and polyadenylation specific factor 7,CPSF7)处于核心位置,为枢纽基因。结论186个差异表达基因和5个模块可以作为儿童MUO的潜在靶标,其中CDC5L、CTPS1、HLA-C和CPSF7基因可能在MUO发生、发展中扮演重要的角色。
Objective To analyze the characteristics of the whole-blood transcriptome of children with metabolically unhealthy obesity(MUO)and metabolically healthy obesity(MHO),in order to find the biomarkers of MUO.Method The GSE146869 data set of Gene Expression Omnibus(GEO)database was used,including the whole-blood transcriptome sequencing data of 27 obese children(13 MHO children and 14 MUO children).The Limma package of R software was used to analyze the differentially expressed genes in the whole-blood cells.Bioinformatics methods such as gene ontology(GO)enrichment analysis,Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis and protein-protein interaction(PPI)network analysis were used to explore the biological functions of differentially expressed genes.Weighted gene co-expression network analysis(WGCNA)was used to cluster differentially expressed genes into modules,and to explore biomarkers or potential therapeutic targets for MUO.Bioinformatics analysis and statistical analysis were performed by R software.Result There was no significant difference in gender,age,body mass index(BMI),systolic blood pressure,diastolic blood pressure,fasting blood glucose,insulin content and insulin resistance index between MHO group and MUO group(all P>0.05).Serum triglyceride,interleukin-6 and tumor necrosis factor-αin MUO group was higher than that in MHO group(all P<0.05).Compared with the MHO group,109 genes were up-regulated and 77 genes were down-regulated in the MUO group.The 186 differentially expressed genes were enriched into 46 GO entries and 3 KEGG pathways.Among the differentially expressed genes,cell division cycle 5 like(CDC5L),CTP synthase 1(CTPS1)and major histocompatibility complex classⅠ-C(HLA-C)genes were the hub genes of PPI network map.In addition,WGCNA clustered 186 differentially expressed genes into 5 modules.In the cyan module,cleavage and polyadenylation specific factor 7(CPSF7)was at the core and was the hub gene.Conclusion 186 differentially expressed genes and 5 modules can be used as potential targets for children with MUO,among which CDC5L,CTPS1,HLA-C and CPSF7 genes may play an essential role in the occurrence and development of MUO.
作者
王青青
张锐锋
葛星
Wang Qingqing;Zhang Ruifeng;Ge Xing(Department of Nephrology and Rheumatology,Xuzhou Children's Hospital,Jiangsu,Xuzhou 221006,China;College of Basic Medicine,Xuzhou Medical University,Jiangsu,Xuzhou 221004,China)
出处
《发育医学电子杂志》
2022年第3期161-167,共7页
Journal of Developmental Medicine (Electronic Version)
基金
江苏省研究生科研与实践创新计划(KYCX20_2445)。
关键词
肥胖
代谢异常型肥胖
代谢正常型肥胖
生物信息学分析
加权基因共表达网络分析
Obesity
Metabolically unhealthy obesity
Metabolically healthy obesity
Bioinformatics analysis
Weighted gene co-expression network analysis
