基于加权基因共表达网络分析筛选儿童神经母细胞瘤中MYCN扩增相关基因

Screening of genes related to MYCN amplification in pediatric neuroblastoma based on Weighted correlation network analysis

目的通过生物信息学分析探究儿童神经母细胞瘤中与MYCN(N-myc)基因相关的共表达基因。方法下载TARGET数据库神经母细胞瘤表达数据共179例,WGCNA分析筛选MYCN扩增共表达基因模块;针对目标基因模块个基因行GO、KEGG富集分析筛选MYCN扩增相关基因可能参与生物过程及信号通路;以MYCN扩增状态将神经母细胞瘤表达数据分为扩增组65例、非扩增组114例,行差异表达基因分析;筛选的差异表达基因同MYCN扩增相关基因取交集后运用K-M法行生存分析(log-rank检验),筛选预后相关基因,Logistics回归探究MYCN扩增状态同预后基因的关系。结果 WGCNA分析提示MEgreenyellow模块同MYCN基因扩增状态相关性最强(R=0.46,P<0.05),为共表达基因,包含基因1 216个,富集分析提示MYCN扩增共表达基因多参与RNA相关通路(RNA的转运、剪切、修饰,RNA相关酶的活性等过程);差异表达基因分析显示,MYCN扩增组相较于非扩增组,基因表达上调47个,表达下调123个;WGCNA分析同差异表达基因取交集筛选出22个关键基因,行生存分析显示同预后相关的基因(P<0.05)有12个,其中DDX1与其他关键基因相关性相对较弱,或为神经母细胞瘤独立预后因素。结论 LINC00839、ATP结合盒亚家族C4(ABCC4)、亚甲基四氢叶酸脱氢酶(NADP+依赖)2(MTHFD2)、磷酸甘油酸脱氢酶(PHGDH)、序列相似性家族13 A(FAM11A)、磷酸丝氨酸转氨酶1 (PSAT1)、假尿苷酸合酶7(PUS7)、DEAD-box解旋酶1(DDX1)、溶质载体有机阴离子转运蛋白家族5A1(SLCO5A1)、Junctophilin 1(JPH1)、溶质载体家族16 1(SLC16A1)、MYCN Opposite Strand(MYCNOS)为神经母细胞瘤中MYCN扩增的共表达基因,与较差的预后相关,是神经母细胞瘤潜在的治疗靶点及预后指标。

Objective Explore the co-expressed genes related to MYCN gene in pediatric neuroblastoma through bioinformatics analysis.Methods Downloaded neuroblastoma expression data of 179 cases from the TARGET database,performed WGCNA analysis to screen MYCN amplification co-expressed gene modules(MEgreenyellow);performed GO and KEGG enrichment analysis for target gene modulesto screen MYCN amplification related genes that may participate in biological processes and signal pathways;according to MYCN amplification status,the neuroblastoma expression data was divided into amplified group(65 cases)and non-amplified group(114 cases),and differentially expressed genes were analyzed.After the selected differentially expressed genes and MYCN amplified related genes were intersected,the survival analysis is performed by K-M method(log-rank)and screened.Prognostic-related genes,logistics regression were used to explore the relationship between MYCN amplification status and prognostic genes.Results WGCNA analysis indicated that the MEgreenyellow module had the strongest correlation with MYCN gene amplification status(R=0.46,P<0.05),including 1216 co-expressed genes.Enrichment analysis indicated that MYCN amplified co-expressed genes were more involved in RNA-related pathways(RNA transfer,shearing,modification,activity of RNA-related enzymes,etc.);differentially expressed gene analysis showed that compared with the non-amplified group,the MYCN amplified group had 47 up-regulated genes and 123 down-regulated genes;22 key genes were selected,survival analysis showed that there were 12 genes related to prognosis(P<0.05).DDX1 has relatively weak correlation with other key genes,is independent of neuroblastoma Prognostic factors.Conclusion LINC00839,ATP binding cassette subfamily C member 4(ABCC4),Methylenetetrahydrofolate dehydrogenase(NADP+dependent)2(MTHFD2),Phosphoglycerate dehydrogenase(PHGDH),Family with sequence similarity 13 member A(FAM13A),Phosphoserine aminotransferase 1(PSAT1),Pseudouridylate synthase 7(PUS7),DEAD-box helicase 1(DDX1),Solute carrier organic anion transporter family member 5A1(SLCO5A1),Junctophilin 1(JPH1),Solute carrier family 16 member 1(SLC16A1),MYCN Opposite Strand(MYCNOS)are the co-expressed genes of MYCN amplification in neuroblastoma,which are associated with poor prognosis and are neuroblasts Potential therapeutic targets and prognostic indicators of tumors.