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基于血管生成相关基因构建克罗恩病诊断和预测英夫利昔单抗无应答的模型。

Constructing models for Crohn's disease diagnosis and prediction of infliximab non-response based on angiogenesis-related genes.

机构信息

School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.

Department of Gastroscopy, Fujian Medical University Affiliated First Quanzhou Hospital, Quanzhou, Fujian, China.

出版信息

Front Immunol. 2024 Jan 26;15:1239496. doi: 10.3389/fimmu.2024.1239496. eCollection 2024.

Abstract

BACKGROUND

Angiogenesis response plays a crucial role in the occurrence and development of Crohn's disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn's disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response.

METHODS

CD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built.

RESULTS

Based on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset.

CONCLUSION

Comprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making.

摘要

背景

血管生成反应在克罗恩病(CD)的发生和发展中起着至关重要的作用,可能涉及英夫利昔单抗无应答的机制。然而,血管生成相关基因在 CD 中的作用尚未得到全面研究。本研究旨在探讨 CD 患者中血管生成相关基因的表达谱,并构建疾病诊断和预测英夫利昔单抗无应答的模型。

方法

从 GEO 数据库中收集与 CD 相关的微阵列数据集。基于差异表达的血管生成相关基因进行无监督共识聚类分析,将 CD 样本分为两个不同的簇。对聚类进行加权基因共表达网络分析(WGCNA),以鉴定血管生成相关模块。基于模块中的差异表达基因,采用机器学习算法进一步识别枢纽基因,并构建疾病诊断模型。随后,从这些枢纽基因中提取与治疗结果相关的基因,并最终构建预测 CD 患者英夫利昔单抗无应答的模型。

结果

基于血管生成相关基因,我们鉴定了两个不同的 CD 簇(C1 和 C2)。与 C1 相比,C2 的代谢途径显著上调,并且存在更多的细胞簇,如 M1 巨噬细胞和浆细胞。此外,C2 对英夫利昔单抗的反应较差。此外,基于枢纽基因构建了预测 CD 患者英夫利昔单抗无应答的模型,并使用外部数据集成功验证。

结论

对血管生成相关基因的综合分析揭示了不同的 CD 簇,它们对英夫利昔单抗的反应率存在差异。模型的构建为疾病诊断和药物选择提供了参考,有助于临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/508c/10853379/90889fd1be95/fimmu-15-1239496-g001.jpg

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