鉴定溃疡性结肠炎中与二硫中毒相关的铁下垂的亚型和生物标志物。

IF 2.7 3区 生物学
Yinghao Jiang, Hongyan Meng, Xin Zhang, Jinguang Yang, Chengxin Sun, Xiaoyan Wang
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引用次数: 0

摘要

背景:二硫下垂和铁下垂是不同的程序性细胞死亡模式,与多种疾病的发生发展密切相关,但与溃疡性结肠炎(UC)的关系尚不清楚。因此,我们的研究旨在探索UC中与二硫中毒相关的铁下垂(DRF)相关的分子亚型和生物标志物。方法:采用Pearson分析对DRF基因进行鉴定。然后,我们根据DRF基因将140份UC样本分为不同的亚型,并探讨它们之间的生物学和临床特征。接下来,通过差异分析和WGCNA算法鉴定中心基因,并使用三种机器学习算法从中心基因中筛选UC的生物标志物。此外,我们分析了免疫细胞生物标志物与转录因子之间的关系,并预测了可能用于治疗UC的天然化合物。最后,我们通过RT-qPCR实验进一步验证了标记的可靠性。结果:经Pearson分析共鉴定出118个DRF基因。根据DRF基因的表达水平,我们将UC患者分为C1和C2亚型,两种亚型在免疫浸润丰度和疾病活动性方面存在显著差异。机器学习算法确定了三种生物标志物,包括XBP1、FH和MAP3K5。进一步分析表明,这三种生物标志物与多种免疫细胞和转录因子密切相关。此外,预测了6种与生物标志物相对应的天然化合物,这可能有助于UC的有效治疗。最后,XBP1、FH和MAP3K5在动物实验中的表达趋势与生物信息学分析结果一致。结论:本研究系统阐明了DRF基因在UC发生发展中的作用,并鉴定出3种潜在的生物标志物,为UC的诊断和治疗提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of subtypes and biomarkers associated with disulfidptosis-related ferroptosis in ulcerative colitis.

Background: Disulfidptosis and ferroptosis are different programmed cell death modes, which are closely related to the development of a variety of diseases, but the relationship between them and ulcerative colitis (UC) is still unclear. Therefore, our study aimed to explore the molecular subtypes and biomarkers associated with disulfidptosis-related ferroptosis (DRF) in UC.

Methods: We used Pearson analysis to identify DRF genes. Then, we classified 140 UC samples into different subtypes based on the DRF genes and explored the biological and clinical characteristics between them. Next, the hub genes were identified by differential analysis and WGCNA algorithms, and three machine learning algorithms were used to screen biomarkers for UC from hub genes. In addition, we analyzed the relationship between biomarkers of immune cells and transcription factors and predicted natural compounds that might be used to treat UC. Finally, we further verified the reliability of the markers by RT-qPCR experiments.

Results: 118 DRF genes were identified using Pearson analysis. Based on the expression level of the DRF genes, we classified UC patients into C1 and C2 subtypes, with significant differences in the abundance of immune infiltration and disease activity between the two subtypes. The machine learning algorithms identified three biomarkers, including XBP1, FH, and MAP3K5. Further analyses revealed that the three biomarkers were closely associated with a variety of immune cells and transcription factors. In addition, six natural compounds corresponding to the biomarkers were predicted, which may contribute to the effective treatment of UC. Finally, the expression trends of XBP1, FH, and MAP3K5 in animal experiments were consistent with the results of bioinformatics analysis.

Conclusion: In this study, we systematically elucidated the role of DRF genes in the development of UC, and identified three potential biomarkers, providing a new idea for the diagnosis and treatment of UC.

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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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