A&R:全转录组学分析识别炎症性和非炎症性主动脉瘤之间的差异基因表达特征

2022-09-07 彼岸河边草 MedSci原创

对手术切除的主动脉组织的炎症性主动脉瘤进行了第一次全转录组学分析,确定了特征基因和生物分子过程,同时发现CIA可能是GCA的有限病症。此外,计算网络分析揭示了药物干预的潜在新策略。

目的使用高通量基因表达谱识别主动脉炎的标志基因和生物分子过程,并通过药物基因组网络分析提供一系列潜在的新药物靶点(基因)和治疗方法。

方法:对手术切除的炎性动脉瘤(伴有或不伴有风湿性多肌痛的巨细胞动脉炎[GCA],n=8;临床孤立性主动脉炎[CIA],n=17)和接受外科主动脉修复术的非炎性动脉瘤(n=25)进行RNA测序。在控制临床协变量的同时,确定了2个患者组之间的差异表达基因 (DEG)。蛋白质-蛋白质相互作用模型、药物-基因靶点信息和DEG用于构建药物基因组网络,以识别有希望的药物靶点和潜在的主动脉炎新治疗策略。

结果总体而言,与任何其他临床特征相比,组织基因表达模式与疾病状态最相关。与非炎症性主动脉瘤相比,研究人员确定了炎症性主动脉瘤中分别显著上调和下调的159个和 93个基因发现上调基因富含免疫相关功能,而下调基因则富含神经元过程。值得注意的是,GCA患者炎症性主动脉瘤的基因表达谱与CIA患者没有差异。最后,药物基因组网络分析确定了可能被目前批准用于其他炎症性疾病的免疫抑制药物靶向的基因。

结论对手术切除的主动脉组织的炎症性主动脉瘤进行了第一次全转录组学分析,确定了特征基因和生物分子过程,同时发现CIA可能是GCA的有限病症。此外,计算网络分析揭示了药物干预的潜在新策略,并为精确诊断和治疗主动脉炎提出了未来的生物标志物发现方向。

出处:Hur B, Koster MJ, Jang JS, Weyand CM, Warrington KJ, Sung J. Global Transcriptomic Profiling Identifies Differential Gene Expression Signatures Between Inflammatory and Noninflammatory Aortic Aneurysms. Arthritis Rheumatol. 2022 Aug;74(8):1376-1386. doi: 10.1002/art.42138. Epub 2022 Jun 20. PMID: 35403833.

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    2023-07-28 mjldent
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