School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China.
Department of Gastroscopy, Fujian Medical University Affiliated First Quanzhou Hospital, Quanzhou, Fujian, China.
Front Immunol. 2024 Jan 26;15:1239496. doi: 10.3389/fimmu.2024.1239496. eCollection 2024.
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.
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.
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.
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.
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。
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。
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。
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。