Identification of SUMOylation-related signature genes associated with immune infiltration in ulcerative colitis through bioinformatics analysis and experimental validation

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-10-10 DOI:10.1016/j.gene.2024.148996

Ying Long , Feihong Huang , Juan Zhang , Jinxiu Zhang , Ruoxi Cheng , Liye Zhu , Qiuling Chen , Dan Yang , Xiaoping Pan , Wenfang Yang , Mengbin Qin , Jiean Huang

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引用次数: 0

Abstract

Objective

Ulcerative colitis (UC) is a chronic inflammatory disorder challenging to diagnose clinically. We focused on identifying and validating SUMOylation-related signature genes in UC and their association with immune infiltration.

Methods

Five eligible gene expression profiles were selected from the Gene Expression Omnibus (GEO) database and merged into a single dataset comprising 260 UC patients and 76 healthy controls (HC). Differentially expressed genes (DEGs) were identified, and these were intersected with SUMOylation-related genes to obtain differentially expressed SUMOylation-related genes (DESRGs). Next, we identify the signature genes and validate them through comprehensive analyses employing GO, KEGG, GSVA, Lasso-cox regression, ROC curves, and clustering analysis. The infiltrating immune cells were analyzed using the CIBERSORT algorithm and Pearson correlation analysis. Finally, in vitro and in vivo experiments validated the identified signature genes.

Results

PALMD, THRB, MAGED1, PARP1, and SLC16A1 were identified. Next, an excellent predictive model for UC was established and distinct subgroups of patients associated with SUMOylation were identified. Moreover, the NF-κB signaling pathway likely plays a pivotal role in the regulation of SUMOylation in UC. Additionally, we validated that the alterations in PALMD, THRB, and MAGED1 expression in LPS-induced Caco-2 cells concurred with our bioinformatics findings, particularly demonstrating statistically significant differences in PALMD and THRB expression. Finally, in a DSS-induced mouse colitis model, we observed a significant upregulation of PALMD expression. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation.

Conclusion

This study comprehensively elucidates the biological roles of SUMOylation-related genes in UC, identifying PALMD, MAGED1, THRB, PARP1, and SLC16A1 as signature genes that represent promising biomarkers for UC diagnosis and prognosis.

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通过生物信息学分析和实验验证，确定与溃疡性结肠炎免疫浸润相关的 SUMOylation 相关特征基因。

目的：溃疡性结肠炎（UC）是一种难以临床诊断的慢性炎症性疾病。我们的研究重点是鉴定和验证 UC 中 SUMOylation 相关特征基因及其与免疫浸润的关系：方法：我们从基因表达总库（GEO）数据库中筛选出五个符合条件的基因表达谱，并将其合并到一个由 260 名 UC 患者和 76 名健康对照（HC）组成的数据集中。确定了差异表达基因（DEGs），并将这些基因与 SUMOylation 相关基因交叉，得到差异表达的 SUMOylation 相关基因（DESRGs）。接下来，我们通过GO、KEGG、GSVA、Lasso-cox回归、ROC曲线和聚类分析等综合分析方法确定特征基因并对其进行验证。利用 CIBERSORT 算法和皮尔逊相关分析对浸润的免疫细胞进行了分析。最后，体外和体内实验验证了确定的特征基因：结果：确定了 PALMD、THRB、MAGED1、PARP1 和 SLC16A1。接着，建立了一个出色的 UC 预测模型，并确定了与 SUMOylation 相关的不同患者亚群。此外，NF-κB 信号通路可能在 UC 的 SUMO 化调控过程中起着关键作用。此外，我们还验证了 LPS 诱导的 Caco-2 细胞中 PALMD、THRB 和 MAGED1 表达的变化与我们的生物信息学研究结果一致，尤其是 PALMD 和 THRB 表达有显著的统计学差异。最后，在 DSS 诱导的小鼠结肠炎模型中，我们观察到了 PALMD 表达的显著上调。由 Aries Systems Corporation 的 Editorial Manager® 和 ProduXion Manager® 提供：本研究全面阐明了 SUMOylation 相关基因在 UC 中的生物学作用，确定了 PALMD、MAGED1、THRB、PARP1 和 SLC16A1 为特征基因，这些基因是 UC 诊断和预后的有前途的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464