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探讨 mA 甲基化调节剂作为晚期脓毒症免疫治疗的表观遗传靶点。

Exploration of mA methylation regulators as epigenetic targets for immunotherapy in advanced sepsis.

机构信息

Tianjin Medical University, Tianjin, 300203, China.

Department of Emergency, Shangjin Nanfu Hospital, West China Hospital, Sichuan University, Chengdu, 610044, Sichuan, China.

出版信息

BMC Bioinformatics. 2023 Jun 17;24(1):257. doi: 10.1186/s12859-023-05379-w.

Abstract

BACKGROUND

This study aims to deeply explore the relationship between mA methylation modification and peripheral immune cells in patients with advanced sepsis and mine potential epigenetic therapeutic targets by analyzing the differential expression patterns of mA-related genes in healthy subjects and advanced sepsis patients.

METHODS

A single cell expression dataset of peripheral immune cells containing blood samples from 4 patients with advanced sepsis and 5 healthy subjects was obtained from the gene expression comprehensive database (GSE175453). Differential expression analysis and cluster analysis were performed on 21 mA-related genes. The characteristic gene was identified based on random forest  algorithm, and the correlation between the characteristic gene METTL16 and 23 immune cells in patients with advanced sepsis was evaluated using single-sample gene set enrichment analysis.

RESULTS

IGFBP1, IGFBP2, IGF2BP1, and WTAP were highly expressed in patients with advanced sepsis and mA cluster B. IGFBP1, IGFBP2, and IGF2BP1 were positively correlated with Th17 helper T cells. The characteristic gene METTL16 exhibited a significant positive correlation with the proportion of various immune cells.

CONCLUSION

IGFBP1, IGFBP2, IGF2BP1, WTAP, and METTL16 may accelerate the development of advanced sepsis by regulating mA methylation modification and promoting immune cell infiltration. The discovery of these characteristic genes related to advanced sepsis provides potential therapeutic targets for the diagnosis and treatment of sepsis.

摘要

背景

本研究旨在通过分析健康受试者和晚期脓毒症患者之间 mA 相关基因的差异表达模式,深入探讨 mA 甲基化修饰与外周免疫细胞之间的关系,并挖掘潜在的表观遗传治疗靶点。

方法

从基因表达综合数据库(GSE175453)中获取包含 4 名晚期脓毒症患者和 5 名健康受试者外周血样本的单个细胞表达数据集,对 21 个 mA 相关基因进行差异表达分析和聚类分析。基于随机森林算法鉴定特征基因,并采用单样本基因集富集分析评估特征基因 METTL16 与晚期脓毒症患者 23 种免疫细胞的相关性。

结果

IGFBP1、IGFBP2、IGF2BP1 和 WTAP 在晚期脓毒症患者和 mA 簇 B 中高表达。IGFBP1、IGFBP2 和 IGF2BP1 与 Th17 辅助 T 细胞呈正相关。特征基因 METTL16 与各种免疫细胞的比例呈显著正相关。

结论

IGFBP1、IGFBP2、IGF2BP1、WTAP 和 METTL16 可能通过调节 mA 甲基化修饰并促进免疫细胞浸润,加速晚期脓毒症的发生发展。这些与晚期脓毒症相关的特征基因的发现为脓毒症的诊断和治疗提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76b/10276409/b37bfd0291ac/12859_2023_5379_Fig1_HTML.jpg

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