目的

本研究旨在分析肾移植术后BKV 肾病免疫细胞浸润情况及关键基因。

方法

从GEO 数据库中获取17 例肾移植后肾组织活检微阵列芯片数据，通过PCA 降维分析、差异表达分析、富集分析、PPI 网络构建与关键基因筛选以及免疫细胞浸润分析等方法并利用wilcoxon 秩和检验和Spearman 相关性分析等统计学方法，探讨BKV 肾病免疫细胞浸润的模式和关键基因，并进一步通过外部数据集GSE75693 进行验证。

结果

研究发现，BKV 肾病活检样本与正常肾移植活检样本和BKV 血症肾组织活检样本在基因表达模式上表现出明显的分离。免疫细胞浸润分析揭示了BKV 相关肾病中的免疫细胞特征，特别是浆细胞、静息肥大细胞、调节性T 细胞和活化NK 细胞比例降低 （P ＜ 0.05），而静息CD4 记忆T 细胞、记忆B 细胞、活化CD4 记忆T 细胞以及静息NK 细胞比例升高 （P ＜ 0.05）。差异表达基因的识别、GO 与KEGG分析以及PPI 网络构建与Hub 基因筛选，揭示了KIF11、DLGAP5、CDK1、CDC20、BUB1、ASPM、KIF20A、BUB1B、TOP2A 和NUSAP1 等关键基因与特定免疫细胞类型的浸润比例呈现出不同程度的相关性 （|r|≥ 0.483，P ＜ 0.05），这些关键基因在BKV 肾病活检样本中表达均上调（|log₂ fold change| ≥1，P ＜ 0.001）。外部数据集验证结果显示，TOP2A、CDC20 以及KIF20A 在BKV 肾病活检样本中上调 （P ＜ 0.05）。

结论

本研究揭示BKV 肾病的免疫细胞浸润模式和分子特征，为理解BKV 肾病的发病机制提供新的视角，并可能为未来的治疗策略提供潜在的靶点。

Objective

This study aims to analyze immune cell infiltration and key genes of in BKV nephropathy after renal transplantation based on transcriptomics.

Methods

We obtained microarray chip data from 17 renal tissue biopsies after renal transplantation from the GEO database.Through PCA dimensionality reduction analysis， differential expression analysis， enrichment analysis，PPI network construction and key gene screening， as well as cell infiltration analysis， combined with statistical methods such as the Wilcoxon ran-sum test and Spearman correlation analysis， we explored the patterns of immune cell infiltration and key genes in BKV nephropathy. The findings were subsequently validated through the external dataset GSE75693.

Results

The study found that biopsy samples from BKV nephropathy showed a distinct separation in gene expression patterns compared to normal renal transplant biopsy samples and BKV viremia renal tissue biopsy samples. Immune cell infiltration analysis revealed immune cell characteristics in BKV-related nephropathy， with significantly reduced proportions of plasma cells， resting mast cells， regulatory T cells， and activated NK cells （P ＜ 0.05）， while the proportions of resting CD4 memory T cells， memory B cells， activated CD4 memory T cells， and resting NK cells were significantly increased （P ＜ 0.05）. Identification of differentially expressed genes， GO and KEGG analyses， and PPI network construction with hub gene screening revealed that key genes such as KIF11， DLGAP5， CDK1， CDC20， BUB1， ASPM，KIF20A， BUB1B， TOP2A， and NUSAP1 showed varying degrees of correlation with the infiltration proportions of specific immune cell types （|r| ≥ 0.483， P ＜ 0.05）. The expression of these key genes was upregulated （|log₂ fold change| ≥ 1， P ＜ 0.001）. Validation results from the external dataset showed that TOP2A， CDC20， and KIF20A were significantly upregulated in BKV nephropathy biopsy samples （P ＜ 0.05）.

Conclusion

This study reveals the immune cell infiltration patterns and molecular characteristics of BKV nephropathy， providing new insights into the pathogenesis of BKV nephropathy and potential targets for future therapeutic strategies.