Wang X-G, Peng Y, Song X-L, Lan J-P
Hematology Department, Zhejiang Provincial People's Hospital, Hangzhou City, China.
Eur Rev Med Pharmacol Sci. 2016 Mar;20(5):810-7.
The study aimed to identify potential therapeutic biomarkers and agents in multiple myeloma (MM) based on bioinformatics analysis.
The microarray data of GSE36474 were downloaded from Gene Expression Omnibus database. A total of 4 MM and 3 normal bone marrow mesenchymal stromal cells (BM-MSCs) samples were used to identify the differentially expressed genes (DEGs). The hierarchical clustering analysis and functional enrichment analysis of DEGs were performed. Furthermore, co-expression network was constructed by Cytoscape software. The potential small molecular agents were identified with Connectivity Map (cMap) database.
A total of 573 DEGs were identified in MM samples comparing with normal samples, including 322 down- and 251 up-regulated genes. The DEGs were separated into two clusters. Down-regulated genes were mainly enriched in cell cycle function, while up-regulated genes were related to immune response. Down-regulated genes such as checkpoint kinase 1 (CHEK1), MAD2 mitotic arrest deficient-like 1 (MAD2L1) and DBF4 zinc finger (DBF4) were identified in cell cycle-related co-expression network. Up-regulated gene of guanylate binding protein 1, interferon-inducible (GBP1) was a hub node in immune response-related co-expression network. Additionally, the small molecular agent vinblastine was identified in this study.
The genes such as CHEK1, MAD2L1, DBF4 and GBP1 may be potential therapeutic biomarkers in MM. Vinblastine may be a potential therapeutic agent in MM.
本研究旨在通过生物信息学分析确定多发性骨髓瘤(MM)潜在的治疗生物标志物和药物。
从基因表达综合数据库下载GSE36474的微阵列数据。共使用4个MM样本和3个正常骨髓间充质基质细胞(BM-MSC)样本鉴定差异表达基因(DEG)。对DEG进行层次聚类分析和功能富集分析。此外,用Cytoscape软件构建共表达网络。通过连通性图谱(cMap)数据库鉴定潜在的小分子药物。
与正常样本相比,MM样本中共鉴定出573个DEG,包括322个下调基因和251个上调基因。这些DEG被分为两个簇。下调基因主要富集在细胞周期功能中,而上调基因与免疫反应相关。在细胞周期相关共表达网络中鉴定出如检查点激酶1(CHEK1)、MAD2有丝分裂阻滞缺陷样1(MAD2L1)和DBF4锌指(DBF4)等下调基因。鸟苷酸结合蛋白1(干扰素诱导)(GBP1)的上调基因是免疫反应相关共表达网络中的一个枢纽节点。此外,本研究中鉴定出小分子药物长春碱。
CHEK1、MAD2L1、DBF4和GBP1等基因可能是MM潜在的治疗生物标志物。长春碱可能是MM的一种潜在治疗药物。