糖基化基因构建的IgA肾病的风险预测模型及免疫浸润分析
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1.南京医科大学附属南京医院 南京市第一医院;2.南京医科大学附属江宁医院

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基金项目:

国家自然科学基金青年项目,No.82000693


Exploration of glycosylation-related genes and immune infiltration analysis of IgA nephropathy
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Department of Nephrology,Nanjing First Hospital,Nanjing Medical University,Nanjing

Fund Project:

Youth Project of National Natural Science Foundation of China, No.82000693

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    摘要:

    目的:IgA肾病(IgA nephropathy,IgAN)糖基化相关基因的筛选及免疫浸润分析。方法:从GEO数据库中下载IgAN数据集,筛选糖基化相关差异基因并进行功能分析,通过LASSO、SVM-RFE和随机森林树算法进一步筛选糖基化相关最优特征基因(the optimal feature genes,OFGs),并运用免疫组织化学染色、蛋白质免疫印迹和Nephroseq v5外部数据库验证OFGs差异表达。基于OFGs绘制IgAN预测列线图,分析免疫细胞浸润,构建ceRNA网络。结果:经过筛选首次报道了三个OFGs(ST8SIA1、CHSY1和PIGH),构建列的线图模型提示OFGs对IgAN发生具备良好的预测价值。免疫细胞浸润分析显示:和对照组相比,IgAN组CD8+T细胞、CD4+幼稚T细胞、活化CD4+记忆T细胞、静息树突状细胞以及静息肥大细胞等浸润显著增加,而幼稚B细胞、浆细胞、静息CD4+记忆T细胞、活化肥大细胞和中性粒细胞等浸润明显减少。OFGs与活化CD4+记忆T细胞、静息CD4+记忆T细胞、CD4+幼稚T细胞、幼稚B细胞等相关。验证实验结果也表明与微小病变性肾病相比,在IgAN中CHSY1和PIGH表达水平显著下降,而ST8SIA1表达水平显著增加。值得注意的是,糖尿病肾病和微小病变性肾病中OFGs的表达水平无统计学差异。此外,我们构建了一个包含117个lncRNA、67个miRNA和3个OFGs的ceRNA网络。结论:ST8SIA1、CHSY1和PIGH可能是诊断和治疗IgAN的潜在靶点,结合浸润细胞免疫和ceRNA网络,为IgAN的研究提供了新的视角。

    Abstract:

    Objective: This study aimed to exploration of glycosylation-related genes and immune infiltration analysis of IgA nephropathy. Methods: IgAN datasets were obtained from the GEO database. We then identified differentially expressed glycosylation-related genes and performed functional enrichment analyses. Next, optimal feature genes (OFGs) were selected using LASSO, SVM-RFE, and Random Forest algorithms. The expression of OFGs in IgAN were validated by immunohistochemistry staining, western blot and the Nephroseq v5 database. OFGs were further used to create a nomogram model, compare immune cell infiltration and construct a ceRNA network. Results: After screening, three OFGs (ST8SIA1, CHSY1 and PIGH) were first reported. The nomogram model showed that OFGs had good predictive value for IgAN occurrence. Compared to normal samples, IgAN showed increased infiltration of CD8+T cells, na?ve CD4+ T cell, memory activated CD4+ T cells, resting dendritic cells, and resting mast cells, while na?ve B cells, plasma cells, activated mast cells, and neutrophils were reduced. OFGs were associated with memory activated CD4+ T cells, memory resting CD4+ T cells, na?ve CD4+ T cell, na?ve B cells among others. The validation experiments also revealed that the expression levels of CHSY1 and PIGH were significantly decreased, while the expression level of ST8SIA1 was significantly increased in IgAN compared with minimal change nephropathy. Of note, the expression levels of OFGs in diabetic nephropathy and minimal change nephropathy were not statistically different. A ceRNA network consisting of 117 lncRNAs, 67 miRNAs, and 3 OFGs was constructed. Conclusion: ST8SIA1, CHSY1, and PIGH were identified as potential targets for diagnosis and treatment of IgAN. In conjunction with immune cell infiltration and ceRNA network, these results offer a novel perspective for future research on IgAN.

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  • 收稿日期:2024-03-21
  • 最后修改日期:2024-09-17
  • 录用日期:2024-11-15
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