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线粒体相关基因 PDK2、CHDH 和 ALDH5A1 可作为溃疡性结肠炎的诊断标志物,并与免疫细胞浸润相关。

Mitochondrial-related genes PDK2, CHDH, and ALDH5A1 served as a diagnostic signature and correlated with immune cell infiltration in ulcerative colitis.

机构信息

Department of Gastroenterology, Guizhou Provincial People’s Hospital, Medical College of Guizhou University, Guiyang, Guizhou, China.

Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China.

出版信息

Aging (Albany NY). 2024 Feb 19;16(4):3803-3822. doi: 10.18632/aging.205561.

Abstract

We conducted an investigation to determine the potential of mitochondrial-related genes as diagnostic biomarkers in ulcerative colitis (UC), while also examining their association with immune cell infiltration. To achieve this, we acquired four datasets pertaining to UC, which included gene expression arrays and clinical data, from the GEO database. Subsequently, we selected three signature genes (PDK2, CHDH, and ALDH5A1) to construct a diagnostic model for UC. The nomogram and ROC curves exhibited exceptional diagnostic efficacy. Following this, quantitative real-time polymerase chain reaction and western blotting assays validated the decreased mRNA and protein expression of PDK2, CHDH, and ALDH5A1 in the model of UC cells and dextran sulfate sodium salt (DSS)-induced mice colitis tissues, aligning with the findings in the risk model. This investigation suggested a negative correlation between the expression of ALDH5A1, CHDH, and PDK2 and the infiltration of M1 macrophages. Then, immunofluorescence analysis confirmed the augmented expression of CD86 in the tissue of mice subjected to DSS, while a diminished expression of ALDH5A1, CHDH, and PDK2 was observed. Consequently, it can be inferred that targeting mitochondria-associated genes, namely PDK2, CHDH, and ALDH5A1, holds potential as a viable strategy for prognostic prediction and the implementation of immune therapy for UC.

摘要

我们进行了一项调查,以确定与线粒体相关的基因作为溃疡性结肠炎(UC)诊断生物标志物的潜力,同时研究它们与免疫细胞浸润的关系。为此,我们从 GEO 数据库中获取了四个与 UC 相关的数据集,包括基因表达谱和临床数据。然后,我们选择了三个特征基因(PDK2、CHDH 和 ALDH5A1)来构建 UC 的诊断模型。列线图和 ROC 曲线显示出出色的诊断效果。随后,定量实时聚合酶链反应和 Western blot 分析验证了 PDK2、CHDH 和 ALDH5A1 在 UC 细胞模型和葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎组织中的 mRNA 和蛋白表达降低,与风险模型中的发现一致。这项研究表明,ALDH5A1、CHDH 和 PDK2 的表达与 M1 巨噬细胞的浸润呈负相关。然后,免疫荧光分析证实了 DSS 处理的小鼠组织中 CD86 的表达增加,而 ALDH5A1、CHDH 和 PDK2 的表达减少。因此,可以推断靶向与线粒体相关的基因,即 PDK2、CHDH 和 ALDH5A1,作为 UC 预后预测和免疫治疗的一种可行策略具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c84/10929806/ed3708debc0b/aging-16-205561-g001.jpg

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