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基于微阵列的胰腺神经内分泌肿瘤基因表达模式分析。

Microarray based analysis of gene expression patterns in pancreatic neuroendocrine tumors.

作者信息

Wang D-D, Liu Z-W, Han M-M, Zhu Z-M, Tu Y-L, Dou C-Q, Jin X, Cai S-W, Du N

机构信息

Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2015 Sep;19(18):3367-74.

Abstract

OBJECTIVE

Pancreatic neuroendocrine tumors (PanNETs) are a small subgroup of tumors with a variety of biological behaviors.

MATERIALS AND METHODS

We sought to identify the specially expressed genes and characterize significant pathways in PanNETs compared with non-neoplastic samples. Gene expression profile GSE43795 was obtained from Gene Expression Omnibus database, which included 6 PanNETs and 5 non-neoplastic samples. The differentially expressed genes (DEGs) were identified using Limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions and pathways of DEGs. Transcription factors (TFs) and tumor-associated genes (TAGs) were also identified. Finally, a protein-protein interaction (PPI) network was constructed, and hub proteins and functional module were screened out.

RESULTS

Total of 821 DEGs (421 down-regulated, 400 up-regulated) were selected. GO and KEGG enrichment analyses showed that up-regulated DEGs were related to several pathways, including type 2 diabetes mellitus, Ca2+ signaling pathway, long-term potentiation, and long-term depression pathways. Down-regulated DEGs were enriched in several pathways, such as pancreatic secretion, protein digestion and absorption, and metabolic pathway. Interferon-stimulated gene protein 15 (ISG15), somatostatin (SST), and synaptosomal-associated protein 25 kDa (SNAP25) were identified as hub proteins.

CONCLUSIONS

The genes involved in type 2 diabetes mellitus pathway may play important roles in the development of PanNETs. SNAP25, SST, and ISG15 may be used as potential targets for treatment of PanNETs.

摘要

目的

胰腺神经内分泌肿瘤(PanNETs)是具有多种生物学行为的一小类肿瘤。

材料与方法

我们试图鉴定PanNETs中特异性表达的基因,并与非肿瘤样本相比,表征其重要通路。从基因表达综合数据库中获取基因表达谱GSE43795,其中包括6个PanNETs样本和5个非肿瘤样本。使用Limma软件包鉴定差异表达基因(DEGs)。采用基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析来富集DEGs的功能和通路。还鉴定了转录因子(TFs)和肿瘤相关基因(TAGs)。最后,构建了蛋白质-蛋白质相互作用(PPI)网络,并筛选出枢纽蛋白和功能模块。

结果

共筛选出821个DEGs(421个下调,400个上调)。GO和KEGG富集分析表明,上调的DEGs与多种通路相关,包括2型糖尿病、Ca2+信号通路、长时程增强和长时程抑制通路。下调的DEGs富集于多种通路,如胰腺分泌、蛋白质消化和吸收以及代谢通路。干扰素刺激基因蛋白15(ISG15)、生长抑素(SST)和突触体相关蛋白25 kDa(SNAP25)被鉴定为枢纽蛋白。

结论

参与2型糖尿病通路的基因可能在PanNETs的发生发展中起重要作用。SNAP25、SST和ISG15可能作为PanNETs治疗的潜在靶点。

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