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疾病持续时间影响克罗恩病的肠道基因表达特征,但不影响性结肠炎
Susanne Ibing1,2,3, Christopher Tastad4, Bernhard Y Renard1,2,3
1Hasso Plattner Institute, Digital Engineering Faculty, University of Potsdam, Potsdam, 14482, Germany.
疾病持续时间在克罗恩病 (CD) 中显著改变肠道基因表达,但不是性结肠炎 (UC). 这些发现可能会导致新的生物标志物和基于疾病持续时间的CD治疗方法.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 疾病持续时间与克罗恩病 (CD) 中治疗效率降低和肠道损伤增加相关,与性结肠炎 (UC) 不同.
- 了解与CD和UC疾病持续时间相关的肠道转录组差异对于向治疗至关重要.
研究的目的:
- 在CD和UC患者中调查与疾病持续时间相关的肠道基因表达变化.
- 确定受炎性肠病 (IBD) 疾病持续时间影响的特定基因和途径.
主要方法:
- 分析了来自CD和UC患者的两个大型,独立的前性队列 (MSCCR和SPARC IBD) 的肠组织RNA测序数据.
- 进行了差异性基因表达和通路分析,以及使用CD患者的叶单细胞RNA测序数据进行细胞类型特定表达分析.
- 在CD队列中,评估了已识别的与疾病持续时间相关的途径与对infliximab的治疗反应的关联.
主要成果:
- 显着更多的基因被差异地表达,与UC相比,CD的疾病持续时间在两个队列中都增加了.
- 在长期的疾病中,发现了一种共享的基因特征,包括263个下调和135个上调的基因.
- 丰富的途径包括氧化酸化,线粒体功能障碍,胆固醇生物合成,LXR/RXR激活和蛋白质修饰. 有四种途径与因弗力西马布无反应有关.
结论:
- 疾病持续时间明显影响CD中的肠道基因表达,UC中观察到的影响较小.
- 鉴定的基因和途径为开发独特的生物标志物和根据CD疾病持续时间量身定制的治疗策略提供了潜力.
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