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生物信息学微阵列分析及与肝硬化肝脏相关的基因表达谱鉴定。

Bioinformatics microarray analysis and identification of gene expression profiles associated with cirrhotic liver.

作者信息

Chan Kun-Ming, Wu Tsung-Han, Wu Ting-Jung, Chou Hong-Shiue, Yu Ming-Chin, Lee Wei-Chen

机构信息

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

Kaohsiung J Med Sci. 2016 Apr;32(4):165-76. doi: 10.1016/j.kjms.2016.03.008. Epub 2016 Apr 23.

Abstract

Cirrhosis is the endpoint of liver fibrosis that is accompanied by limited regeneration capacity and complications and is the ultimate cause of death in many patients. Despite this, few studies have thoroughly looked at the gene expression profiles in the cirrhotic liver. Hence, this study aims to identify the genes that were differentially expressed in the cirrhotic liver and to explore the putative related signaling pathway and interaction networks. The gene expression profiles of cirrhotic livers and noncirrhotic livers were examined and compared using microarray gene analysis. Proteins encoded by the differentially expressed genes were analyzed for functional clustering and signaling pathway involvement using MetaCore bioinformatics analyses. The Gene Ontology analysis as well as the Kyoto encyclopedia of Genes and Genomes pathway analysis were also performed. A total of 213 significant genes were differentially expressed at more than a two-fold change in cirrhotic livers as compared to noncirrhotic livers. Of these, 105 upregulated genes and 63 downregulated genes were validated through MetaCore bioinformatics analyses. The signaling pathways and major functions of proteins encoded by these differentially expressed genes were further analyzed; results showed that the cirrhotic liver has a unique gene expression pattern related to inflammatory reaction, immune response, and cell growth, and is potentially cancer related. Our findings suggest that the microarray analysis may provide clues to the molecular mechanisms of liver cirrhosis for future experimental studies. However, further exploration of areas regarding therapeutic strategy might be possible to support metabolic activity, decrease inflammation, or enhance regeneration for liver cirrhosis.

摘要

肝硬化是肝纤维化的终末期,伴有有限的再生能力和并发症,是许多患者死亡的最终原因。尽管如此,很少有研究全面观察过肝硬化肝脏中的基因表达谱。因此,本研究旨在鉴定在肝硬化肝脏中差异表达的基因,并探索可能相关的信号通路和相互作用网络。使用微阵列基因分析检查并比较了肝硬化肝脏和非肝硬化肝脏的基因表达谱。使用MetaCore生物信息学分析对差异表达基因编码的蛋白质进行功能聚类和信号通路参与情况分析。还进行了基因本体分析以及京都基因与基因组百科全书通路分析。与非肝硬化肝脏相比,肝硬化肝脏中共有213个显著基因差异表达,变化超过两倍。其中,通过MetaCore生物信息学分析验证了105个上调基因和63个下调基因。进一步分析了这些差异表达基因编码的蛋白质的信号通路和主要功能;结果表明,肝硬化肝脏具有与炎症反应、免疫反应和细胞生长相关的独特基因表达模式,并且可能与癌症相关。我们的研究结果表明,微阵列分析可能为未来实验研究提供肝硬化分子机制的线索。然而,关于治疗策略方面可能需要进一步探索,以支持代谢活动、减轻炎症或增强肝硬化的再生能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42f6/11916604/18d9f49b72d6/KJM2-32-165-g003.jpg

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