Zhu Yidong, Jin Xiaoyi, Liu Jun, Yang Wenzhong
Department of Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Traditional Chinese Medicine, Fengxian District Nanqiao Community Health Center, Shanghai, 201400, China.
Biochem Genet. 2024 May 27. doi: 10.1007/s10528-024-10831-4.
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.
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的潜在关键基因，并评估它们在临床应用中的功能作用。从基因表达综合数据库中获取FL患者的微阵列数据和临床特征。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的关键基因。进行功能富集分析以研究这些关键基因在FL中的潜在作用。进行孟德尔随机化（MR）分析以验证顶级基因对FL风险的因果效应。此外，进行基因集富集分析（GSEA）和免疫细胞分析以阐明关键基因在FL中的作用机制。通过差异表达分析和WGCNA分别鉴定出1363个差异表达基因和157个中心基因，从而确定了117个重叠基因作为FL的关键基因。功能富集分析显示免疫相关途径与FL之间存在显著相关性。MR分析仅显示T细胞受体相关蛋白激酶70（ZAP70）的ζ链与FL风险之间存在显著关联，其他顶级基因未观察到显著关联。GSEA和免疫细胞分析表明，ZAP70可能通过免疫相关途径参与FL的发生和发展。通过整合生物信息学和MR分析，成功鉴定并验证了ZAP70作为一种有前景的FL生物标志物。功能研究表明免疫相关途径与FL之间存在显著相关性。这些发现对FL诊断和治疗靶点的识别具有重要意义，并为FL潜在的分子机制提供了有价值的见解。
