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基因表达谱的综合分析挖掘出风湿性疾病的共同标志物。

Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

作者信息

Wang Lan, Wu Long-Fei, Lu Xin, Mo Xing-Bo, Tang Zai-Xiang, Lei Shu-Feng, Deng Fei-Yan

机构信息

Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, P. R. China.

出版信息

PLoS One. 2015 Sep 9;10(9):e0137522. doi: 10.1371/journal.pone.0137522. eCollection 2015.

Abstract

OBJECTIVE

Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.

METHODS

We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis.

RESULTS

We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation.

CONCLUSION

The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.

摘要

目的

风湿性疾病有一些共同症状。迄今为止积累的广泛基因表达研究已成功分别鉴定出每种风湿性疾病的特征性分子。然而,风湿性疾病之间是否存在共同因素尚待检验。

方法

我们收集并利用了6个公共微阵列数据集,涵盖4种代表性风湿性疾病,包括类风湿关节炎、系统性红斑狼疮、强直性脊柱炎和骨关节炎。然后我们检测了各数据集之间差异表达基因的重叠情况,并进行了荟萃分析,旨在鉴定区分病理病例和正常对照的共同差异表达基因。为了进一步深入了解所鉴定的共同差异表达基因的功能,我们进行了基因本体富集分析和蛋白质-蛋白质相互作用分析。

结果

我们共鉴定出8个差异表达基因(肿瘤坏死因子配体超家族成员10、CX3趋化因子受体1、淋巴细胞抗原96、Toll样受体5、硫氧还蛋白、TIA1蛋白、蛋白激酶C eta型、穿孔素1),每个基因与4种研究的风湿性疾病中的至少3种相关。荟萃分析证实了这8个基因的显著性,并突出了4个基因(CX3CR1、LY96、TLR5和PRF1)的普遍显著性。蛋白质-蛋白质相互作用和基因本体富集分析表明,这8个基因相互作用以发挥与免疫反应和免疫调节相关的功能。

结论

这些发现支持风湿性疾病存在共同因素。对于类风湿关节炎、系统性红斑狼疮、强直性脊柱炎和骨关节炎疾病,这些共同因素包括TNFSF10、CX3CR1、LY96、TLR5、TXN、TIA1、PRKCH和PRF1。对这些共同因素的深入研究可能为理解发病机制和制定风湿性疾病干预策略提供关键线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba49/4564267/4670989356d9/pone.0137522.g001.jpg

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