摘要
目的探讨葡萄膜黑色素原位瘤与转移瘤差异表达基因及其作用;探索乳腺癌1号基因相关蛋白1(BAP1)缺失的葡萄膜黑色素瘤(UM)差异表达基因以及预测BAP1靶标,探讨BAP1缺失对UM转移作用及其机制。方法生信分析筛选UM转移差异表达基因及其功能,对公共数据库GEO中的数据集GSE27831,GSE48863以及GSE39171中芯片数据以2为底数进行对数转换以及标准化(P<0.05,|logFC|>1)等预处理。为了进一步捕捉术语之间的关系,选择丰富的术语的子集,并将其作为网络图绘制,其中相似性>0.3的项由边缘连接。我们从20个簇中的每个簇中选择具有最佳P值的项,约束每个集群不超过15个术语,总共不超过250个术语。该网络用CytoSCAPE可视化插件,其中每个节点表示1个丰富的术语,并用其簇的名称着色。对于每个给定的基因列表,利用以下数据库进行蛋白质-蛋白质相互作用富集分析:BioGrid、InWeb_IM、OmniPath。所得到的网络至少包含与另一个列表成员形成交互的蛋白质子集。如果网络中包含3~500个蛋白质,则进一步应用分子复合检测(MCODE)算法来识别紧密连接的网络组件。路径和过程富集分析被独立地应用于每个MCODE组件,并且保留3个最佳评分(按P值,P<0.05,FDR<0.001生物途径视为有价值)术语作为对应组件的功能描述。结果我们运用生物信息学技术对转移性和非转移性UM组织样本和BAP1沉默和正常表达UM细胞样本基于微阵列对基因组数据进行基因本体富集(GO)分析和京都基因和基因组百科全书(KEGG)分析,结果显示差异基因主要富集在补体凝血级联途径。结论 BAP1在转移性UM的异常低表达,UM中BAP1突变可能通过影响肿瘤血管生成促进肿瘤浸润转移。
Objective To investigate the differentially expressed genes and their roles in uveal melanoma(UM in situ and metastasis. To explore differentially expressed genes in UM with BAP1 deletion. To predict the BAP1 targeting gene to explore the metastasis effect and mechanisms of BAP1 deletion in UM. Methods The differentially expressed UM genes and their functions were screened by bioinformatics technology analysis. The data sets GSE27831, GSE48863 and GSE39171 in the public database GEO were logarithmically with base 2 converted and standardized. After that, the relationship between terms was further captured, a rich subset of terms was selected and drawn as a network graph. Items with the best P value were selected to obtain subsets of less than 250 terms, and the subset was drawn with the CytoSCAPE visual plug-in. The list of differentially expressed genes was analyzed for protein-protein interaction enrichment by using the following databases: BioGrid, InWeb_IM, OmniPath. The resulting network contained a subset of proteins that interact with another list member at least. Molecular Compound Detection(MCODE) algorithm was applied to identify tightly connected network components, and three best scoring terms(according to P value) were retained as functional descriptions of corresponding components. Results Using bioinformatics technology, metastatic and non-metastatic UM tissue samples, BAP1 silenced and normal UM cell samples were analyzed by GO and KEGG analysis based on microarray. The results showed that the differential genes were mainly concentrated in complement coagulation cascade pathway. Conclusion The expression of BAP1 was abnormally low in metastatic UM. The mutation of BAP1 in UM was predicted to affect angiogenesis and promoted invasion and metastasis of tumors by regulating complement coagulation cascade pathway.
作者
聂爱芹
谢宁
李强
李伟
Nie Aiqin;Xie Ning;Li Qiang;Li Wei(Ophthalmology, Shenzhen People′s Hospital & Second Clinical Medical College of Jinan University, Guangdong 030001, China)
出处
《山西医药杂志》
CAS
2019年第13期1523-1526,共4页
Shanxi Medical Journal
基金
2018年度广东省医学科研基金立项项目(B2018139)
