Common Marker Genes Identified from Various Sample Types for Systemic Lupus Erythematosus.

Common Marker Genes Identified from Various Sample Types for Systemic Lupus Erythematosus.
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从系统性红斑狼疮的各种样本类型中鉴定出的常见标记基因

DOI:
10.1371/journal.pone.0156234
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Deng FY
Deng FY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bing PF;Xia W;Wang L;Zhang YH;Lei SF;Deng FY

文献摘要

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目的系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病。已进行基因表达研究以鉴定各种类型样品中的SLE相关基因。目前尚不清楚是否存在与SLE相关但与样本类型无关的共同标记基因,这些基因可能具有后续翻译研究的潜力。本研究的目的是在不同类型的SLE样本中识别共同的标志基因。方法基于4个公开的SLE基因表达谱芯片数据集,包括3种代表性的血源性样本(单核细胞、外周血单核细胞(PBMC)和全血),利用3个统计量(fold-change,FC; t-test p值; false-discovery rate adjusted p值)对不同样本类型中SLE同时调控的基因进行分析。对于常见的标记基因,我们进行了基因本体富集分析和蛋白质相互作用分析,以了解其功能。结果筛选出10个与SLE相关的常见标志基因(IFI 6、IFI 27、IFI 44 L、OAS 1、OAS 2、EIF 2AK 2、PLSCR 1、STAT 1、RNASE 2和GSTO 1)。在所有研究的样本类型中均观察到SLE患者的IFI 6、IFI 27和IFI 44 L显著上调,尽管与PBMC和全血相比,单核细胞中的FC最显著(8.82-251.66 vs. 3.73-74.05 vs. 1.19-1.87)。在上述10个基因中,除RNASE 2和GSTO 1外,有8个基因相互作用,并与已知的SLE易感基因相互作用,参与免疫应答、RNA和蛋白质催化以及细胞死亡。结论不同类型SLE患者存在共同的标志基因。本文确定的10个常见标志物基因值得进行后续研究,以确定它们作为预测SLE或治疗反应的诊断或治疗标志物的潜力。
Objective Systemic lupus erythematosus (SLE) is a complex auto-immune disease. Gene expression studies have been conducted to identify SLE-related genes in various types of samples. It is unknown whether there are common marker genes significant for SLE but independent of sample types, which may have potentials for follow-up translational research. The aim of this study is to identify common marker genes across various sample types for SLE. Methods Based on four public microarray gene expression datasets for SLE covering three representative types of blood-born samples (monocyte; peripheral blood mononuclear cell, PBMC; whole blood), we utilized three statistics (fold-change, FC; t-test p value; false discovery rate adjusted p value) to scrutinize genes simultaneously regulated with SLE across various sample types. For common marker genes, we conducted the Gene Ontology enrichment analysis and Protein-Protein Interaction analysis to gain insights into their functions. Results We identified 10 common marker genes associated with SLE (IFI6, IFI27, IFI44L, OAS1, OAS2, EIF2AK2, PLSCR1, STAT1, RNASE2, and GSTO1). Significant up-regulation of IFI6, IFI27, and IFI44L with SLE was observed in all the studied sample types, though the FC was most striking in monocyte, compared with PBMC and whole blood (8.82–251.66 vs. 3.73–74.05 vs. 1.19–1.87). Eight of the above 10 genes, except RNASE2 and GSTO1, interact with each other and with known SLE susceptibility genes, participate in immune response, RNA and protein catabolism, and cell death. Conclusion Our data suggest that there exist common marker genes across various sample types for SLE. The 10 common marker genes, identified herein, deserve follow-up studies to dissert their potentials as diagnostic or therapeutic markers to predict SLE or treatment response.