Functional investigation and two-sample Mendelian randomization study of primary biliary cholangitis hub genes.

IF 1 4区 医学 Q3 MEDICINE, GENERAL & INTERNAL World Journal of Clinical Cases Pub Date : 2024-10-26 DOI:10.12998/wjcc.v12.i30.6391
Yun-Chuan Yang, Xiang Ma, Chi Zhou, Nan Xu, Ding Ding, Zhong-Zheng Ma, Lei Zhou, Pei-Yuan Cui
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Abstract

Background: The identification of specific gene expression patterns is crucial for understanding the mechanisms underlying primary biliary cholangitis (PBC) and finding relevant biomarkers for diagnosis and therapeutic evaluation.

Aim: To determine PBC-associated hub genes and assess their clinical utility for disease prediction.

Methods: PBC expression data were obtained from the Gene Expression Omnibus database. Overlapping genes from differential expression analysis and weighted gene co-expression network analysis (WGCNA) were identified as key genes for PBC. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses were performed to explore the potential roles of key genes. Hub genes were identified in protein-protein interaction (PPI) networks using the Degree algorithm in Cytoscape software. The relationship between hub genes and immune cells was investigated. Finally, a Mendelian randomization study was conducted to determine the causal effects of hub genes on PBC.

Results: We identified 71 overlapping key genes using differential expression analysis and WGCNA. These genes were primarily enriched in pathways related to cytokine-cytokine receptor interaction, and Th1, Th2, and Th17 cell differentiation. We utilized Cytoscape software and identified five hub genes (CD247, IL10, CCL5, CCL3, and STAT3) in PPI networks. These hub genes showed a strong correlation with immune cell infiltration in PBC. However, inverse variance weighting analysis did not indicate the causal effects of hub genes on PBC risk.

Conclusion: Hub genes can potentially serve as valuable biomarkers for PBC prediction and treatment, thereby offering significant clinical utility.

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原发性胆汁性胆管炎中心基因的功能调查和双样本孟德尔随机研究
背景:确定特定的基因表达模式对于了解原发性胆汁性胆管炎(PBC)的发病机制以及寻找诊断和治疗评估的相关生物标记物至关重要:目的:确定与原发性胆汁性胆管炎(PBC)相关的枢纽基因,并评估其在疾病预测中的临床实用性:方法:从基因表达总库数据库中获取PBC表达数据。从差异表达分析和加权基因共表达网络分析(WGCNA)中确定重叠基因为 PBC 的关键基因。为探索关键基因的潜在作用,进行了京都基因和基因组百科全书以及基因本体分析。利用Cytoscape软件中的Degree算法在蛋白质-蛋白质相互作用(PPI)网络中识别了枢纽基因。研究了枢纽基因与免疫细胞之间的关系。最后,进行了孟德尔随机化研究,以确定枢纽基因对 PBC 的因果效应:我们利用差异表达分析和 WGCNA 发现了 71 个重叠的关键基因。这些基因主要富集在与细胞因子-细胞因子受体相互作用以及 Th1、Th2 和 Th17 细胞分化相关的通路中。我们利用 Cytoscape 软件确定了 PPI 网络中的五个中心基因(CD247、IL10、CCL5、CCL3 和 STAT3)。这些中心基因与 PBC 的免疫细胞浸润有很强的相关性。然而,逆方差加权分析并未表明枢纽基因对 PBC 风险有因果效应:枢纽基因有可能成为预测和治疗 PBC 的有价值的生物标志物,从而提供重要的临床实用性。
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World Journal of Clinical Cases
World Journal of Clinical Cases Medicine-General Medicine
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期刊介绍: The World Journal of Clinical Cases (WJCC) is a high-quality, peer reviewed, open-access journal. The primary task of WJCC is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of clinical cases. In order to promote productive academic communication, the peer review process for the WJCC is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJCC are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in clinical cases.
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