Identification of hub fatty acid metabolism-related genes and immune infiltration in IgA nephropathy.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-11-14 DOI:10.1080/0886022X.2024.2427158
Xiaoqian Qian, Shuyang Bian, Qin Guo, Dongdong Zhu, Fan Bian, Yinhui Song, Gengru Jiang
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Abstract

Aims: To investigate the potential mechanisms of fatty acid metabolism (FAM)-related genes in IgA nephropathy (IgAN) and to explore its immune cell infiltration characteristic.

Methods: Datasets for IgAN and FAM-related genes were obtained from GEO and MSigDB database, respectively. We employed differential expression analysis and WGCNA to identify common genes. GO and KEGG analyses were performed to compare the differences between IgAN and control groups. Furthermore, LASSO logistic regression was applied to develop a predictive model based on FAM-related genes. The efficacy of this prognostic model was evaluated using ROC analysis. The infiltration of immune cells and immune-related functions were assessed with CIBERSORT tool. Finally, the identified key genes were validated in blood samples from IgAN and control patients, as well as in human mesangial cells (HMCs) following Gd-IgA stimulation using Real-time PCR.

Results: A total of 12 hub genes linked to FAM were identified in patients with IgAN. A predictive model consisting of four genes was conducted through COX and LASSO regression analysis, revealing AUC values that indicate a relatively strong diagnostic capability. Immune infiltration analysis indicated that various immune cells have significant associations with IgAN. Additionally, Real-time PCR assays confirmed that the expression levels of hub genes were markedly reduced in IgAN patients and in Gd-IgA treated HMCs compared to controls.

Conclusion: This study employed bioinformatics methods to unveiled the immune cell infiltration associated with IgAN and to explore the potential genetic connection between FAM and IgAN. This could aid in predicting the risk of IgAN and enhance both diagnosis and prognosis of this condition.

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鉴定 IgA 肾病中枢脂肪酸代谢相关基因和免疫浸润。
目的:研究脂肪酸代谢(FAM)相关基因在IgA肾病(IgAN)中的潜在作用机制,并探讨其免疫细胞浸润特征:IgAN和FAM相关基因的数据集分别来自GEO和MSigDB数据库。我们采用差异表达分析和 WGCNA 来识别常见基因。我们进行了 GO 和 KEGG 分析,以比较 IgAN 组和对照组之间的差异。此外,我们还应用 LASSO 逻辑回归建立了一个基于 FAM 相关基因的预测模型。利用 ROC 分析评估了该预后模型的有效性。利用 CIBERSORT 工具评估了免疫细胞的浸润和免疫相关功能。最后,利用实时 PCR 技术在 IgAN 患者和对照组患者的血液样本中,以及在 Gd-IgA 刺激后的人类间质细胞(HMCs)中验证了所确定的关键基因:结果:在 IgAN 患者中总共发现了 12 个与 FAM 相关的中枢基因。通过 COX 和 LASSO 回归分析,建立了一个由四个基因组成的预测模型,其 AUC 值表明该模型具有较强的诊断能力。免疫浸润分析表明,各种免疫细胞与 IgAN 有显著关联。此外,实时 PCR 检测证实,与对照组相比,IgAN 患者和经 Gd-IgA 处理的 HMC 中枢纽基因的表达水平明显降低:本研究采用生物信息学方法揭示了与IgAN相关的免疫细胞浸润,并探索了FAM与IgAN之间的潜在遗传联系。这有助于预测 IgAN 的发病风险,提高诊断和预后效果。
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来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
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