神经病理性疼痛差异表达基因的筛选及生物学功能分析

关键词：神经病理性疼痛  差异表达基因  生物信息学

Keywords:neuropathic pain  differentially expressed genes  bioinformatics

摘要：

      摘要 目的：通过生物信息学方法分析正常人与坐骨神经痛患者数据，从而筛选出神经病理性疼痛（neuropathic pain， NP）的潜在差异基因。 方法：从基因表达数据库下载芯片数据GSE150408。用R软件的limma包筛选差异表达基因（differentially expressed genes，DEGs），使用clusterProfiler包进行基因本体论（gene ontology，GO）富集分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路分析，通过STRING数据库进行DEGs蛋白互作网络分析。 结果：共筛选得到424个DEGs，包括233个上调基因和191个下调基因。GO富集分析表明DEGs主要分布在囊泡、分泌性颗粒、第三粒等细胞组分；参与防御反应、免疫调节过程、细胞激活、白细胞激活等生物学过程，同时发挥免疫受体激活、补体激活、MAP激酶磷酸化等分子功能。KEGG通路分析表明DEGs主要集中在癌症中的转录失调等通路；基因集富集分析（gene set enrichment analysis， GSEA）最显著富集的基因集为细胞内吞作用，疱疹病毒感染等。蛋白互作网络中上调蛋白FCGR1A的度值最高，下调蛋白SPTBN2的度值最高，这2个蛋白是关键节点。 结论：NP的外周血液具有炎症和免疫特征，AZU1、BPI、FCGR1A、SPTBN2等4个基因是参与NP的关键基因。

Abstract:

      Abstract Objective： To investigate differentially expressed genes （DEGs） for neuropathic pain between sciatica and healthy controls. Method： The microarray dataset GSE150408 were downloaded from gene expression database （gene expression omnibus database，GEO）. The DEGs were screened using the limma V3.42.0（linear models for microarray data） package of the R software program（version 3.5.0）. GEO terms and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis of DEGs were automatically completed and visualized by the clusterProiler V3.14.0. STRING was searched to identify and predict interactions between genes or proteins， to construct the protein to protein interaction. Result： A total of 424 DEGs were screened， including 233 up-regulated genes and 191 down-regulated genes. The result of GO enrichment indicated that for biological process， DEGs were significantly enriched in defense response， regulation of immune system process， cell activation， leukocyte activation. Regarding cell components， DEGs were significantly enriched in vesicles， secretory granules， tertiary granule. For molecular function， DEGs were significantly enriched in immune receptor activation， complement receptor activity and MAP kinase phosphatase activity. The result of KEGG pathway-enrichment indicated that DEGs were mainly enriched in transcriptional misregulation in cancer. Moreover， the GSEA analysis indicated that the most significant enriched gene sets included endocytosis， Epstein-Barr virus infection. PPI analysis were performed to explore the potential function of the DEGs. It showed that the degree of FCGR1A was the highest in up-regulated proteins and the highest in down-regulated proteins. These two proteins were the key nodes. Conclusion： It showed an inflammatory and immune characteristic in peripheral blood for neuropathic pain. AZU1， BPI， FCGR1A and SPTBN2 were the key genes in neuropathic pain.