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利用生物信息学分析鉴定良性前列腺增生中的关键基因

Identification of key genes in benign prostatic hyperplasia using bioinformatics analysis.

作者信息

Xiang Peng, Liu Dan, Guan Di, Du Zhen, Hao Yongxiu, Yan Wei, Wang Mingdong, Ping Hao

机构信息

Department of Urology, Beijing Tongren Hospital, Capital Medical University, No1. Dongjiaomingxiang Street, Dongcheng District, Beijing, 100730, China.

Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University and Capital Medical University, Beijing Tongren Hospital, Beijing, 100730, China.

出版信息

World J Urol. 2021 Sep;39(9):3509-3516. doi: 10.1007/s00345-021-03625-5. Epub 2021 Feb 9.

Abstract

PURPOSE

This study aimed to identify differentially expressed genes (DEGs) and pathways in benign prostatic hyperplasia (BPH) by comprehensive bioinformatics analysis.

METHODS

Data of the gene expression microarray (GSE6099) were downloaded from GEO database. DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction network was constructed through STRING. Anterior gradient 2 (ARG2) and lumican (LUM) staining in paraffin-embedded specimens from BPH and normal prostate (NP) were detected by immunohistochemistry (IHC). Differences between groups were analyzed by the Student's t test.

RESULTS

A total of 24 epithelial DEGs and 39 stromal DEGs were determined. The GO analysis results showed that epithelial DEGs between BPH and NP were enriched in biological processes of glucose metabolic process, glucose homeostasis and negative regulation of Rho protein signal transduction. For DEGs in stroma, enriched biological processes included response to ischemia, antigen processing and presentation, cartilage development, T cell costimulation and energy reserve metabolic process. ARG2, as one of the epithelial DEGs, was mainly located in epithelial cells of prostate. In addition, LUM is primarily expressed in the stroma. We further confirmed that compared with NP, the BPH have the lower ARG2 protein level (p = 0.029) and higher LUM protein level (p = 0.003) using IHC.

CONCLUSIONS

Our study indicated that there are possible differentially expressed genes in epithelial and stromal cells, such as ARG2 and LUM, which may provide a novel insight for the pathogenesis of BPH.

摘要

目的

本研究旨在通过全面的生物信息学分析,鉴定良性前列腺增生(BPH)中差异表达基因(DEG)和信号通路。

方法

从基因表达综合数据库(GEO)下载基因表达微阵列(GSE6099)数据。通过GEO2R获取DEG。使用DAVID数据库对选定基因进行功能和富集分析。通过STRING构建蛋白质-蛋白质相互作用网络。采用免疫组织化学(IHC)检测BPH和正常前列腺(NP)石蜡包埋标本中的前梯度2(ARG2)和亮氨酸蛋白聚糖(LUM)染色。采用学生t检验分析组间差异。

结果

共确定了24个上皮DEG和39个基质DEG。基因本体(GO)分析结果表明,BPH和NP之间的上皮DEG在葡萄糖代谢过程、葡萄糖稳态和Rho蛋白信号转导负调控的生物学过程中富集。对于基质中的DEG,富集的生物学过程包括对缺血的反应、抗原加工和呈递、软骨发育、T细胞共刺激和能量储备代谢过程。ARG2作为上皮DEG之一,主要位于前列腺上皮细胞中。此外,LUM主要在基质中表达。我们进一步通过IHC证实,与NP相比,BPH的ARG2蛋白水平较低(p = 0.029),LUM蛋白水平较高(p = 0.003)。

结论

我们的研究表明,上皮细胞和基质细胞中可能存在差异表达基因,如ARG2和LUM,这可能为BPH的发病机制提供新的见解。

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