School of Medicine, Nankai University, Tianjin, PR China; No.94 Weijin Road, Nankai District, Tianjin, 300073, PR China; Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
Crit Rev Eukaryot Gene Expr. 2022;32(2):11-24. doi: 10.1615/CritRevEukaryotGeneExpr.2021038904.
Immune imbalance has become an important factor in the progression of chronic kidney disease (CKD). Molecular typing of CKD may be key to achieving precise treatment. xCell allows immune cell phenotyping in CKD. We integrated two independent microarray datasets and divided 87 CKD patients into two subgroups using unsupervised consensus clustering to study the correlation between CKD and patient sex, age, and CKD stage. We found different expression patterns and clinical characteristics between the two groups. CKD stage was more advanced in cluster I than in cluster II, and the weighted gene coexpression network analysis module characteristics showed enrichment of interferon and leukocyte-associated immune pathways in cluster I. Differentially expressed gene analysis revealed the 12 most significantly changed genes, of which sirtuin 1 (SIRT1) was significantly downregulated in cluster I. Gene set enrichment analysis identified multiple immune-related processes involved in CKD. xCell immune infiltration analysis revealed the significant upregulation of natural killer T (NKT) cells and the significant downregulation of most T and B cell types in cluster I. SIRT1 showed a significant negative correlation with NKT cell infiltration but a positive correlation with CD4+ T cell and natural killer cell infiltration. We systematically studied the molecular typing of the CKD transcriptome and estimated the degree of immune cell infiltration based on molecular subtypes. Our results indicate that different subgroups may have unique gene expression patterns and immune dysregulation patterns, thus providing a basis for precise treatment and immune research in CKD.
免疫失衡已成为慢性肾脏病(CKD)进展的重要因素。CKD 的分子分型可能是实现精准治疗的关键。xCell 可实现 CKD 中的免疫细胞表型分析。我们整合了两个独立的微阵列数据集,并使用无监督共识聚类将 87 名 CKD 患者分为两个亚组,以研究 CKD 与患者性别、年龄和 CKD 分期之间的相关性。我们发现两组之间存在不同的表达模式和临床特征。与聚类 II 相比,聚类 I 中的 CKD 分期更为晚期,加权基因共表达网络分析模块特征显示聚类 I 中干扰素和白细胞相关免疫途径富集。差异表达基因分析揭示了 12 个变化最显著的基因,其中 SIRT1 在聚类 I 中显著下调。基因集富集分析确定了多个涉及 CKD 的免疫相关过程。xCell 免疫浸润分析显示聚类 I 中自然杀伤 T(NKT)细胞显著上调,大多数 T 细胞和 B 细胞类型显著下调。SIRT1 与 NKT 细胞浸润呈显著负相关,与 CD4+T 细胞和自然杀伤细胞浸润呈显著正相关。我们系统地研究了 CKD 转录组的分子分型,并根据分子亚型估计了免疫细胞浸润的程度。我们的研究结果表明,不同亚组可能具有独特的基因表达模式和免疫失调模式,从而为 CKD 的精准治疗和免疫研究提供了依据。