Bioinformatics reveals TNFAIP6 as a candidate gene and suggests its potential crosstalk in the treatment of hemodialysis in chronic kidney disease

Hemodialysis (HD) is a life-sustaining treatment for chronic kidney disease (CKD) patients. This study aimed to identify candidate diagnostic biomarkers associated with HD-treated CKD. The public dataset was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) showing opposite trends across the three groups were obtained as crosstalk genes, and their potential pathways were explored through KEGG and GSEA analyses. Next, hub genes were identified using LASSO regression, and their diagnostic potential was assessed <i>via</i> ROC analysis. Key immune cell populations were identified using ssGSEA. Blood samples from healthy controls (<i>n</i> = 10), CKD patients (<i>n</i> = 9), and HD-treated CKD patients (<i>n</i> = 7) were collected to validate hub gene expression. A total of 132 crosstalk genes were identified, with the TGF-β and KRAS signaling pathways potentially activated in the HD group. Two hub genes, SIK1 and TNFAIP6, exhibited AUC values exceeding 0.8 for diagnosing CKD and HD-treated CKD groups. Compared to the other groups, neutrophil abundance was significantly higher in CKD group and showed a strong correlation with the hub genes. External datasets and RT-qPCR validated a consistent expression trend of TNFAIP6. Therefore, TNFAIP6 may represent a potential candidate gene with biomarker relevance in CKD and HD-treated CKD. TNFAIP6 has been previously associated with the TGF-β pathway and neutrophil regulation, and its crosstalk mechanism in HD-treated CKD warrants further exploration.

血液透析（Hemodialysis, HD）是慢性肾病（chronic kidney disease, CKD）患者的一种维持生命的治疗方法。本研究旨在鉴定与HD治疗的CKD相关的候选诊断生物标志物。该公共数据集获取自基因表达综合数据库（Gene Expression Omnibus）。在三组中呈现相反趋势的差异表达基因（differentially expressed genes, DEGs）被确定为交叉对话基因，并通过KEGG和GSEA分析探索其潜在通路。随后，利用LASSO回归（LASSO regression）鉴定枢纽基因，并通过受试者工作特征（Receiver Operating Characteristic, ROC）分析评估其诊断潜力。利用单样本基因集富集分析（single-sample Gene Set Enrichment Analysis, ssGSEA）鉴定关键免疫细胞群。收集健康对照组（n=10）、CKD患者（n=9）和HD治疗的CKD患者（n=7）的血液样本，以验证枢纽基因的表达。共鉴定出132个交叉对话基因，其中TGF-β和KRAS信号通路在HD组中可能被激活。两个枢纽基因SIK1和TNFAIP6在诊断CKD和HD治疗的CKD组中表现出超过0.8的AUC值。与其他组相比，CKD组的中性粒细胞丰度显著升高，且与枢纽基因呈强相关性。外部数据集和实时荧光定量聚合酶链反应（reverse transcription-quantitative Polymerase Chain Reaction, RT-qPCR）验证了TNFAIP6的一致表达趋势。因此，TNFAIP6可能是CKD和HD治疗的CKD中具有生物标志物相关性的潜在候选基因。TNFAIP6此前已被证实与TGF-β通路和中性粒细胞调控相关，其在HD治疗的CKD中的交叉对话机制值得进一步探索。