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溃疡性结肠炎中的氧化应激基因表达:对结肠癌生物标志物发现的意义

Oxidative stress gene expression in ulcerative colitis: implications for colon cancer biomarker discovery.

作者信息

Yan Ting, Su Ting, Zhu Miaomiao, Qing Qiyuan, Huang Binjie, Liu Jun, Ma Tenghui

机构信息

Department of Clinical Nutrition, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, Guangdong, China.

Department of Traditional Chinese Medicine, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, Guangdong, China.

出版信息

Sci Rep. 2025 Jul 2;15(1):22641. doi: 10.1038/s41598-025-05108-8.

Abstract

There is a complex interrelationship between colorectal cancer (CRC) and ulcerative colitis (UC). This study aimed to identify key molecules and pathways involved in the co-occurrence of CRC and UC, as well as the role of oxidative stress in disease progression, through bioinformatics analysis of public RNA sequencing databases. We downloaded datasets from public repositories and conducted gene set enrichment analysis (GSEA), screening for oxidative stress-related differentially expressed genes (OXSRDEGs) to evaluate their diagnostic potential. Subsequently, we performed Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) analyses, followed by immune infiltration analysis using the single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT algorithms. By constructing a multivariate Cox prognostic model using Kaplan-Meier curves and least absolute shrinkage and selection operator (LASSO) regression analysis, we assessed the model's prognostic capability. Furthermore, we utilized the STRING database and Cytoscape to establish a protein-protein interaction (PPI) network and constructed an mRNA-transcription factor (TF) and mRNA-miRNA interaction networks. The molecular functions and signaling pathways enriched in OXSRDEGs were determined. The robust diagnostic efficacy of OXSRDEGs was verified. This analysis suggests that immune cells may collaborate with OXSRDEGs to impact the onset and progression of diseases. A total of 6 OXSRDEGs with prognostic significance were identified, and the multifactorial Cox regression model constructed demonstrated a strong clinical predictive capacity. The mRNA-transcription factor (TF) and mRNA-miRNA interaction networks revealed that OXSRDEGs are regulated by multiple miRNAs and many transcription factors. Common biomarkers of oxidative stress in the pathogenesis, disease progression, gene expression, and transcription of ulcerative colitis and colorectal cancer have been identified, presenting potential therapeutic targets. The model may be beneficial in prognostic prediction and guiding treatment decisions.

摘要

结直肠癌(CRC)与溃疡性结肠炎(UC)之间存在复杂的相互关系。本研究旨在通过对公共RNA测序数据库进行生物信息学分析,确定参与CRC和UC共同发生的关键分子和途径,以及氧化应激在疾病进展中的作用。我们从公共数据库下载数据集并进行基因集富集分析(GSEA),筛选与氧化应激相关的差异表达基因(OXSRDEGs)以评估其诊断潜力。随后,我们进行了基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,接着使用单样本基因集富集分析(ssGSEA)和CIBERSORT算法进行免疫浸润分析。通过使用Kaplan - Meier曲线和最小绝对收缩和选择算子(LASSO)回归分析构建多变量Cox预后模型,我们评估了该模型的预后能力。此外,我们利用STRING数据库和Cytoscape建立了蛋白质 - 蛋白质相互作用(PPI)网络,并构建了mRNA - 转录因子(TF)和mRNA - miRNA相互作用网络。确定了OXSRDEGs中富集的分子功能和信号通路。验证了OXSRDEGs强大的诊断效能。该分析表明免疫细胞可能与OXSRDEGs协同作用影响疾病的发生和进展。共鉴定出6个具有预后意义的OXSRDEGs,构建的多因素Cox回归模型显示出强大的临床预测能力。mRNA - 转录因子(TF)和mRNA - miRNA相互作用网络表明OXSRDEGs受多种miRNA和许多转录因子调控。已确定溃疡性结肠炎和结直肠癌发病机制、疾病进展、基因表达和转录过程中氧化应激的常见生物标志物,为潜在治疗靶点。该模型可能有助于预后预测和指导治疗决策。

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