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外周血细胞的全面 RNA 测序分析揭示了特发性膜性肾病具有潜在生物标志物的差异表达特征。

Comprehensive RNA-Sequencing Analysis in Peripheral Blood Cells Reveals Differential Expression Signatures with Biomarker Potential for Idiopathic Membranous Nephropathy.

机构信息

Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.

Department of Laboratory Medical Center, General Hospital of Northern Theater Command, Shenyang, People's Republic of China.

出版信息

DNA Cell Biol. 2019 Nov;38(11):1223-1232. doi: 10.1089/dna.2019.4701. Epub 2019 Sep 30.

Abstract

To date, the clinical course of idiopathic membranous nephropathy (iMN) remains unclear and lacks direct and effective diagnostic methods. To better understand the host gene expression changes involved in the iMN process and identify the potential signatures for clinical diagnosis, we performed a whole genome-wide transcriptome profile of peripheral blood cells (PBC) from patients with iMN and healthy controls (HCs). A total of 188 differentially expressed genes (DEGs) were detected in patients with iMN versus HCs. Gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these DEGs were mainly correlated with protein targeting, ion homeostasis GO terms, and ribosome and phagosome pathways. The top 10 differentially expressed protein-coding genes with >2-fold changes and high expression levels were validated using quantitative real-time PCR, and showed high consistency with the high-throughput sequencing results. , and genes were selected for further validation and showed the most significant difference between the iMN and HC group, indicating that they could be used as potential clinical diagnostic biomarkers. Our results provide novel potential diagnostic signatures for iMN and have important implications for better understanding the pathogenesis of iMN.

摘要

迄今为止,特发性膜性肾病(iMN)的临床病程仍不清楚,缺乏直接有效的诊断方法。为了更好地了解 iMN 过程中涉及的宿主基因表达变化,并确定潜在的临床诊断特征,我们对 iMN 患者和健康对照(HC)的外周血细胞(PBC)进行了全基因组转录组谱分析。与 HCs 相比,iMN 患者中检测到 188 个差异表达基因(DEGs)。基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路分析表明,这些 DEGs 主要与蛋白靶向、离子动态平衡 GO 术语以及核糖体和吞噬体途径相关。使用定量实时 PCR 验证了前 10 个差异表达蛋白编码基因,这些基因的变化倍数大于 2 倍且表达水平较高,与高通量测序结果具有高度一致性。选择进一步验证的基因,它们在 iMN 和 HC 组之间表现出最显著的差异,表明它们可作为潜在的临床诊断生物标志物。我们的研究结果为 iMN 提供了新的潜在诊断特征,对更好地理解 iMN 的发病机制具有重要意义。

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