肾移植术后BKV肾病免疫细胞浸润及关键基因分析  

Transcriptomic analysis of immune cell infiltration and key genes in BKV nephropathy post-renal transplantation

作　　者：唐敏英 邬绿莹 陈津[2] 路君 吴仲秋 Tang Minying;Wu Lvying;Chen Jin;Lu Jun;Wu Zhongqiu(Fujian Provincial Key Laboratory of Transplantation Biology,the 900th Hospital,Fujian Medical University,Fuzhou 350025,China;Institute of Clinical Medicine,the Second Affiliated Hospital of Hainan Medical University,Haikou 570311,China;Department of Ultrasound,the 900th Hospital,Fujian Medical University,Fuzhou 350025,China;Laboratory of Basic Medicine,the 900th Hospital,Fujian Medical University,Fuzhou 350025,China)

机构地区：[1]福建医科大学福总临床学院(第九〇〇医院)福建省移植生物学重点实验室,福州350025 [2]福建医科大学福总临床学院(第九〇〇医院)超声诊断科,福州350025 [3]福建医科大学福总临床学院(第九〇〇医院)基础医学实验室,福州350025 [4]海南医科大学第二附属医院临床医学研究所,海口570311

出　　处：《中华细胞与干细胞杂志(电子版)》2025年第1期12-19,共8页Chinese Journal of Cell and Stem Cell(Electronic Edition)

基　　金：第九〇〇医院临床应用研究课题(2020L28)福建省移植生物学重点实验室(2014SZ001)。

摘　　要：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 pathog

关 键 词：BK 病毒 免疫细胞浸润 肾移植 BK 病毒性肾病 转录组学 

分 类 号：R69[医药卫生—泌尿科学]