滤泡性淋巴瘤 (FL) 是最常见的惰性淋巴瘤类型，起源于淋巴滤泡内的生发中心 B 细胞。然而，这种疾病的潜在机制仍不清楚。本研究旨在确定 FL 的潜在中心基因并评估其在临床应用中的功能作用。 FL 患者的微阵列数据和临床特征来自基因表达综合数据库。采用差异表达分析和加权基因共表达网络分析（WGCNA）来探索 FL 的枢纽基因。进行功能富集分析以研究这些枢纽基因在 FL 中的潜在作用。进行孟德尔随机化 (MR) 分析以验证主要基因对 FL 风险的因果影响。此外，还进行了基因集富集分析（GSEA）和免疫细胞分析，以阐明 FL 关键基因的相关机制。通过差异表达分析和WGCNA分别鉴定出总共1363个差异表达基因和157个中心基因，从而产生117个重叠基因被认为是FL的中心基因。功能富集分析揭示了免疫相关通路与 FL 之间的显着相关性。 MR 分析显示，仅 T 细胞受体相关蛋白激酶 70 (ZAP70) 的 zeta 链与 FL 风险之间存在显着关联，而其他顶级基因则没有观察到显着关联。 GSEA和免疫细胞分析表明ZAP70可能通过免疫相关途径参与FL的发生和进展。通过整合生物信息学和 MR 分析，ZAP70 被成功鉴定并验证为一种有前途的 FL 生物标志物。功能研究表明免疫相关途径与 FL 之间存在显着相关性。这些发现对于确定 FL 诊断和治疗的靶点具有重要意义，并为 FL 的分子机制提供了宝贵的见解。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可，该公司是施普林格自然。

Follicular lymphoma (FL), the most common type of indolent lymphoma, originates from germinal center B cells within the lymphoid follicle. However, the underlying mechanisms of this disease remain unclear. This study aimed to identify the potential hub genes for FL and evaluate their functional roles in clinical applications. Microarray data and clinical characteristics of patients with FL were obtained from the Gene Expression Omnibus database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to explore hub genes for FL. Functional enrichment analysis was performed to investigate the potential roles of these hub genes in FL. Mendelian randomization (MR) analysis was performed to verify the causal effect of the top genes on FL risk. In addition, gene set enrichment analysis (GSEA) and immune cell analysis were performed to elucidate the involved mechanisms of the crucial genes in FL. A total of 1363 differentially expressed genes and 157 central genes were identified by differential expression analysis and WGCNA, respectively, resulting in 117 overlapping genes considered as hub genes for FL. Functional enrichment analysis revealed significant correlations between immune-related pathways and FL. MR analysis revealed a significant association only between zeta chain of T-cell receptor-associated protein kinase 70 (ZAP70) and FL risk, with no significance observed for the other top genes. GSEA and immune cell analysis suggested that ZAP70 may be involved in the development and progression of FL through immune-related pathways. By integrating bioinformatics and MR analyses, ZAP70 was successfully identified and validated as a promising FL biomarker. Functional investigations indicated a significant correlation between immune-related pathways and FL. These findings have important implications for the identification of targets for the diagnosis and treatment of FL and provide valuable insights into the molecular mechanisms underlying FL.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.