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参与肝缺血再灌注损伤发病机制的潜在RNA结合蛋白的诊断与分子特征分析

Diagnosis and Molecular Characterization of Potential RNA Binding Protein Involved in the Pathogenesis of Liver Ischemia Reperfusion Injury.

作者信息

Lai Weiju, Yu Jiajian, Wen Diguang

机构信息

Central Laboratory, Chongqing FuLing Hospital, School of Medicine, Chongqing University, Chongqing, People's Republic of China.

Department of Hepatobiliary, Chongqing Fuling Hospital, School of Medicine, Chongqing University, Chongqing, People's Republic of China.

出版信息

J Inflamm Res. 2024 Jul 22;17:4881-4893. doi: 10.2147/JIR.S468828. eCollection 2024.

Abstract

BACKGROUND

Liver ischemia-reperfusion is one of the common complications after liver surgery. Uncontrolled liver ischemia-reperfusion will lead to many serious consequences such as surgical failure. It is an urgent clinical problem to search for diagnostic markers and explore its potential pathogenesis.

METHODS

In this study, we focus on 1411 candidate RNA binding protein. Through several GEO (Gene Expression Omnibus) online datasets, we construct a diagnostic model and perform interactive validation. We evaluate the efficacy of the prognostic model. Using bioinformatics methods, we predicted the relevant signaling pathways of liver ischemia-reperfusion and key genes. We also evaluated the association of RNA binding protein with immune cell infiltration. Single cell sequencing datasets were used to explore the expression profiles of key genes at the single cell level. Machine learning algorithm is used to predict key gene RNA binding domains.

RESULTS

ROC (Receiver Operating Characteristic) and DCA (Decision Curve Analysis) curves showed that the above diagnostic model had good and stable diagnostic efficacy and clinical practicability. We identified three key genes (BTG2, CCNL1 and DNAJB1) in liver ischemia-reperfusion. DNAJB1, BTG2 and CCNL1 are mainly expressed in immune cells such as macrophages and T cells, and are closely related to inflammatory pathways such as TNF-α, highlighting their importance in hepatic ischemia reperfusion. We identified RNA-binding domains of the above three genes. We found that the expression of DNAJB1, CCNL1 and BTG2 in the ischemia-reperfusion group were significantly higher than those in the sham operation group.

CONCLUSION

Our study revealed the importance of the candidate RNA binding protein in liver ischemia reperfusion injury and provided new insights into the therapeutic of hepatic ischemia-reperfusion injury.

摘要

背景

肝脏缺血再灌注是肝脏手术后常见的并发症之一。不受控制的肝脏缺血再灌注会导致许多严重后果,如手术失败。寻找诊断标志物并探索其潜在发病机制是一个紧迫的临床问题。

方法

在本研究中,我们聚焦于1411个候选RNA结合蛋白。通过几个基因表达综合数据库(GEO)在线数据集,构建诊断模型并进行交互验证。我们评估预后模型的疗效。使用生物信息学方法,预测肝脏缺血再灌注的相关信号通路和关键基因。我们还评估了RNA结合蛋白与免疫细胞浸润的关联。利用单细胞测序数据集在单细胞水平探索关键基因的表达谱。使用机器学习算法预测关键基因的RNA结合结构域。

结果

受试者工作特征曲线(ROC)和决策曲线分析(DCA)曲线表明,上述诊断模型具有良好且稳定的诊断效能和临床实用性。我们在肝脏缺血再灌注中鉴定出三个关键基因(BTG2、CCNL1和DNAJB1)。DNAJB1、BTG2和CCNL1主要在巨噬细胞和T细胞等免疫细胞中表达,并且与肿瘤坏死因子-α等炎症通路密切相关,突出了它们在肝脏缺血再灌注中的重要性。我们鉴定了上述三个基因的RNA结合结构域。我们发现缺血再灌注组中DNAJB1、CCNL1和BTG2的表达明显高于假手术组。

结论

我们的研究揭示了候选RNA结合蛋白在肝脏缺血再灌注损伤中的重要性,并为肝脏缺血再灌注损伤的治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a05/11278829/23a33ad8b1f3/JIR-17-4881-g0001.jpg

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