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基于基因表达谱的垂体腺瘤发病机制分析

Pathogenesis analysis of pituitary adenoma based on gene expression profiling.

作者信息

Wang Weimin, Xu Zhiming, Fu Li, Liu Wei, Li Xingang

机构信息

School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China ; Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.

Department of Neurosurgery, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China.

出版信息

Oncol Lett. 2014 Dec;8(6):2423-2430. doi: 10.3892/ol.2014.2613. Epub 2014 Oct 13.

Abstract

The aim of the current study was to investigate the pathogenesis of pituitary adenoma through screening of the differentially-expressed genes (DEGs) and proteins in normal pituitary and pituitary adenoma tissues, and analyzing the interactions among them. Following the acquisition of gene expression profiling data from a public functional genomics data repository, Gene Expression Omnibus, DEGs were screened in normal pituitary and pituitary adenoma tissues. Upregulated and downregulated DEGs were further identified through gene ontology functional enrichment analysis. Subsequently, the DEGs were mapped to the Search Tool for the Retrieval of Interacting Genes database, and the protein-protein interaction (PPI) networks of the upregulated and downregulated DEGs were constructed. Finally, the functional modules of the PPI network of the downregulated DEGs were analyzed. In total, 211 upregulated and 413 downregulated DEGs were screened between the normal pituitary and pituitary adenoma samples. Downregulated DEGs were associated with certain functions, including the immune response, hormone regulation and cell proliferation. Upregulated genes were associated with cation transport functions. Five modules were acquired from the PPI network of the downregulated DEGs. Transcription factors, including signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), B-cell lymphoma 6 protein, early growth response 1, POU1F1, jun B proto-oncogene and FOS were the core nodes in the functional modules. In summary, the DEGs and proteins were identified through screening gene expression profiling and PPI networks. The results of the present study indicated that low expression levels of hormone- and immune-related genes facilitated the occurrence of pituitary adenoma. Low expression levels of IL-6 and STAT3 were significant in the dysimmunity of pituitary adenoma. Furthermore, the low expression level of POU1F1 contributed to the reduction in pituitary hormone secretion.

摘要

本研究的目的是通过筛选正常垂体组织和垂体腺瘤组织中差异表达的基因(DEGs)和蛋白质,并分析它们之间的相互作用,来探究垂体腺瘤的发病机制。从公共功能基因组学数据库基因表达综合数据库(Gene Expression Omnibus)获取基因表达谱数据后,在正常垂体组织和垂体腺瘤组织中筛选DEGs。通过基因本体功能富集分析进一步鉴定上调和下调的DEGs。随后,将DEGs映射到检索相互作用基因的搜索工具数据库,构建上调和下调DEGs的蛋白质-蛋白质相互作用(PPI)网络。最后,分析下调DEGs的PPI网络的功能模块。在正常垂体和垂体腺瘤样本之间总共筛选出211个上调的DEGs和413个下调的DEGs。下调的DEGs与某些功能相关,包括免疫反应、激素调节和细胞增殖。上调基因与阳离子转运功能相关。从下调DEGs的PPI网络中获得了五个模块。转录因子,包括信号转导和转录激活因子3(STAT3)、白细胞介素6(IL-6)、B细胞淋巴瘤6蛋白、早期生长反应1、POU1F1、原癌基因jun B和FOS是功能模块中的核心节点。总之,通过筛选基因表达谱和PPI网络鉴定了DEGs和蛋白质。本研究结果表明,激素和免疫相关基因的低表达促进了垂体腺瘤的发生。IL-6和STAT3的低表达在垂体腺瘤的免疫失调中具有重要意义。此外,POU1F1的低表达导致垂体激素分泌减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d2a/4214395/43ebab762bf8/OL-08-06-2423-g01.jpg

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