Ⅰ型神经纤维瘤病发生与恶变相关基因的生物信息学数据分析

The bioinformatic analysis of genes in pathogenesis and malignancy of neurofibromatosis type 1

目的筛选Ⅰ型神经纤维瘤病(NF1)中参与神经性纤维瘤发生和恶变的调控基因。方法从GEO公开数据库获取NF1相关的基因表达数据集(GSE14038)和甲基化表达数据集(E-GEOD21714),其中GSE14038包含正常对照组10例、良性神经纤维瘤组48例和恶性外周神经鞘膜瘤组19例,E-GEOD21714包含正常对照组6例、良性神经纤维瘤组10例、恶性外周神经鞘膜组10例。对不同样本的基因表达进行分析,寻找差异表达的基因,并使用基因注释(GO)、通路富集分析和蛋白质互作分析(PPI)工具对数据进行处理。结果在结合比对了数据库中的差异表达基因和甲基化差异后,与正常对照组相比,良性神经性纤维瘤组中有14个基因可能为神经纤维瘤发生相关调控基因,恶性外周神经鞘膜瘤组中有105个基因可能为恶变相关调控基因。GO分析结果显示,良性神经性纤维瘤组差异基因主要功能为以DNA为模板的转录正向调控、转录因子结合,并主要定位于纺锤体微管,恶性神经性纤维瘤组差异基因主要功能为细胞增殖调控、特定DNA序列的结合,并主要定位于神经源细胞胞体。通路富集分析显示,良性神经性纤维瘤组差异基因主要富集于鞘脂代谢,恶性神经性纤维瘤组差异基因主要富集于轴索导引。针对差异基因的PPI分析示编码蛋白主要位于干细胞发育,其中PAX3、PTGS2、SNAI2、MBP和NOG是排名前5的关联节点基因。结论PAX3可能与神经纤维瘤的发生有关,而PTGS2、SNAI2、MBP和NOG可能与恶性外周神经鞘膜瘤的恶变有关。

Objective To screen regulatory genes of neurofibromatosis type 1(NF1)involved in occurring and malignancy.Methods The NF1-related gene expression data set(GSE14038)and methylation expression data set(E-GEOD21714)were obtained from the GEO public database.According to their sample sources,10 cases were classified as normal samples and 48 cases were benign neurofibroma group and 19 cases of malignant peripheral nerve sheath tumor.The gene expression of different samples was analyzed to identify the differentially expressed genes,and the data were processed by applying gene annotation(GO),pathway enrichment analysis and protein interaction analysis(PPI)tools.Results After comparing difference of gene expression and methylation.in the database,compared with normal group,there were 14 genes in the benign neurofibroma group that might be related to the occurrence of neurofibroma,and 105 genes in the malignant peripheral nerve sheath tumor group that might be related to malignant transformation.The main functions of the differential gene in the benign neurofibromatosis group are positive regulation of DNA dependent/directed transcription,transcription factor binding and mainly located in the spindle microtubules.The main function of the differential gene in the malignant neurofibroma group is regulation of cell proliferation,sequence-specific DNA binding and mainly located in the cell body of neuron.According to pathway enrichment analysis,the differential genes in the benign neurofibroma group were mainly enriched in sphingolipid metabolism,and the differential genes in the malignant neurofibroma group were mainly enriched in axonal guidance.Protein-protein interaction analysis of differential genes showed that the encoded proteins are mainly located in stem cell development,of which PAX3,PTGS2,SNAI2,MBP and NOG are the top 5 related expressed hub genes.Conclusions PAX3 may be related to the occurrence of neurofibromatosis,while PTGS2,SNAI2,MBP and NOG may be related to the malignant transformation of MPNST.