Wang Shuhong, Li Zhongda, Wang Xiao, Zhou Jiexue, Meng Shandong, Zhuang Jinyang, Zhou Yan, Zhao Qin, Zhu Chunli, Zhang Yusheng, Shen Sheng
Department of Neurology, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Avenue West, Tianhe District, Guangzhou, 510632, Guangdong, China.
Department of Organ Transplantation, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, No. 466, Xingang Middle Road, Haizhu District, Guangzhou, 510317, Guangdong, China.
Sci Rep. 2025 May 16;15(1):17060. doi: 10.1038/s41598-025-01049-4.
Ischemic stroke (IS) is a leading global cause of mortality and disability, particularly prominent in patients with end-stage renal disease (ESRD). Despite clinical evidence of their comorbidity, the molecular mechanisms underlying their interaction remain elusive. This study aims to identify shared biomarkers, gene regulatory networks, and therapeutic targets through integrative bioinformatics analyses. Gene expression datasets for IS (GSE16561, GSE22255) and ESRD (GSE37171, GSE142153) were obtained from gene expression omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differential expression genes (DEGs) analysis identified shared genes and enriched pathways. Protein-protein interaction networks were constructed using STRING with clustering algorithms. Immune cell infiltration analysis was performed via CIBERSORT. Transcriptional regulatory networks were predicted using RcisTarget and miRcode. Key gene expressions were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in clinical samples. We identified 417 intersecting genes through WGCNA and 1712 shared differentially expressed genes. Among these, seven key genes (MRPL49, MRPS2, MRPS9, MRPS10, MRPS11, MRPS27, TFB1M) demonstrated central roles in mitochondrial function. Immune infiltration analysis revealed significant correlations with T cells and neutrophils. Pathway enrichment implicated these genes in transforming growth factor beta (TGF-β) signaling, p53 pathway, and G2/M checkpoint. Clinical validation confirmed significant downregulation of MRPS9, MRPS10, MRPS11, MRPS27 and TFB1M in comorbid patients. This study systematically elucidates the mitochondrial-immune interaction mechanisms in IS-ESRD comorbidity, highlighting the pivotal role of mitochondrial ribosomal protein (MRP) family genes in regulating cellular energetics and inflammatory responses. These findings provide new foundations for targeted therapies.
缺血性中风（IS）是全球死亡和残疾的主要原因，在终末期肾病（ESRD）患者中尤为突出。尽管有临床证据表明它们存在合并症，但其相互作用的分子机制仍不清楚。本研究旨在通过综合生物信息学分析确定共同的生物标志物、基因调控网络和治疗靶点。从基因表达综合数据库（GEO）中获取了IS（GSE16561、GSE22255）和ESRD（GSE37171、GSE142153）的基因表达数据集。加权基因共表达网络分析（WGCNA）和差异表达基因（DEG）分析确定了共同基因和富集通路。使用STRING和聚类算法构建蛋白质-蛋白质相互作用网络。通过CIBERSORT进行免疫细胞浸润分析。使用RcisTarget和miRcode预测转录调控网络。通过逆转录定量聚合酶链反应（RT-qPCR）在临床样本中验证关键基因表达。我们通过WGCNA鉴定出417个相交基因和1712个共同差异表达基因。其中，7个关键基因（MRPL49、MRPS2、MRPS9、MRPS10、MRPS11、MRPS27、TFB1M）在线粒体功能中发挥核心作用。免疫浸润分析显示与T细胞和中性粒细胞有显著相关性。通路富集表明这些基因参与转化生长因子β（TGF-β）信号通路、p53通路和G2/M检查点。临床验证证实合并症患者中MRPS9、MRPS10、MRPS11、MRPS27和TFB1M显著下调。本研究系统地阐明了IS-ESRD合并症中的线粒体-免疫相互作用机制，突出了线粒体核糖体蛋白（MRP）家族基因在调节细胞能量代谢和炎症反应中的关键作用。这些发现为靶向治疗提供了新的基础。
