Xuelin He, Yichen Wu, Guanghui Ying, Min Xia, Qien He, Zhaogui Chen, Qiao Zhang, Li Liu, Xia Liu, Yongtao Li
{"title":"通过加权基因共表达网络分析和单细胞转录组分析鉴定和验证糖尿病肾病三羧酸循环相关的诊断生物标志物。","authors":"Xuelin He, Yichen Wu, Guanghui Ying, Min Xia, Qien He, Zhaogui Chen, Qiao Zhang, Li Liu, Xia Liu, Yongtao Li","doi":"10.1007/s00592-025-02557-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is a prevalent and serious complication of diabetes, characterized by high incidence and significant morbidity. Despite growing evidence that the tricarboxylic acid (TCA) cycle plays a crucial role in DN progression, the diagnostic potential of TCA-related genes has yet to be fully explored.</p><p><strong>Methods: </strong>This study began by analyzing the GSE131882 dataset to reveal the expression patterns of TCA-related genes in various renal cell types and to identify genes that differ in expression between high and low subgroups. The GSE30122 dataset was then examined to identify genes with differential expression in DN. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were applied to pinpoint TCA-related gene modules. Following this, multiple machine learning techniques were employed to analyze the TCA gene set that showed differential expression at both cellular and sample levels, allowing us to identify the hub genes. A diagnostic model was constructed, with its effectiveness validated through ROC analysis. The immune landscape of DN was assessed using ssGSEA. GeneMANIA and NetworkAnalyst were also utilized to predict genes with similar functions, as well as miRNAs and transcription factors (TFs) that may regulate these diagnostic genes. Finally, single-cell RNA sequencing (scRNA-seq) data confirmed the expression patterns of these genes.</p><p><strong>Results: </strong>Two TCA-related genes, HPGD and G6PC, were identified as potential diagnostic markers for DN. ROC analysis demonstrated that these genes and their predictive model exhibited strong diagnostic performance in both training and validation cohorts. Immune landscape analysis revealed a more active immune microenvironment in DN patients compared to controls. Additionally, 59 miRNAs and 15 TFs were predicted to regulate the expression of HPGD and G6PC, along with 20 functionally related genes. scRNA-seq data highlighted that HPGD and G6PC are predominantly expressed in glomerular and proximal tubular cells.</p><p><strong>Conclusion: </strong>Two reliable TCA-related biomarkers were pinpointed, potentially advancing early diagnosis and management of DN.</p>","PeriodicalId":6921,"journal":{"name":"Acta Diabetologica","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification and validation of tricarboxylic acid cycle-related diagnostic biomarkers for diabetic nephropathy via weighted gene co-expression network analysis and single-cell transcriptome analysis.\",\"authors\":\"Xuelin He, Yichen Wu, Guanghui Ying, Min Xia, Qien He, Zhaogui Chen, Qiao Zhang, Li Liu, Xia Liu, Yongtao Li\",\"doi\":\"10.1007/s00592-025-02557-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diabetic nephropathy (DN) is a prevalent and serious complication of diabetes, characterized by high incidence and significant morbidity. Despite growing evidence that the tricarboxylic acid (TCA) cycle plays a crucial role in DN progression, the diagnostic potential of TCA-related genes has yet to be fully explored.</p><p><strong>Methods: </strong>This study began by analyzing the GSE131882 dataset to reveal the expression patterns of TCA-related genes in various renal cell types and to identify genes that differ in expression between high and low subgroups. The GSE30122 dataset was then examined to identify genes with differential expression in DN. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were applied to pinpoint TCA-related gene modules. Following this, multiple machine learning techniques were employed to analyze the TCA gene set that showed differential expression at both cellular and sample levels, allowing us to identify the hub genes. A diagnostic model was constructed, with its effectiveness validated through ROC analysis. The immune landscape of DN was assessed using ssGSEA. GeneMANIA and NetworkAnalyst were also utilized to predict genes with similar functions, as well as miRNAs and transcription factors (TFs) that may regulate these diagnostic genes. Finally, single-cell RNA sequencing (scRNA-seq) data confirmed the expression patterns of these genes.</p><p><strong>Results: </strong>Two TCA-related genes, HPGD and G6PC, were identified as potential diagnostic markers for DN. ROC analysis demonstrated that these genes and their predictive model exhibited strong diagnostic performance in both training and validation cohorts. Immune landscape analysis revealed a more active immune microenvironment in DN patients compared to controls. Additionally, 59 miRNAs and 15 TFs were predicted to regulate the expression of HPGD and G6PC, along with 20 functionally related genes. scRNA-seq data highlighted that HPGD and G6PC are predominantly expressed in glomerular and proximal tubular cells.</p><p><strong>Conclusion: </strong>Two reliable TCA-related biomarkers were pinpointed, potentially advancing early diagnosis and management of DN.</p>\",\"PeriodicalId\":6921,\"journal\":{\"name\":\"Acta Diabetologica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Diabetologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00592-025-02557-5\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Diabetologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00592-025-02557-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Identification and validation of tricarboxylic acid cycle-related diagnostic biomarkers for diabetic nephropathy via weighted gene co-expression network analysis and single-cell transcriptome analysis.
Background: Diabetic nephropathy (DN) is a prevalent and serious complication of diabetes, characterized by high incidence and significant morbidity. Despite growing evidence that the tricarboxylic acid (TCA) cycle plays a crucial role in DN progression, the diagnostic potential of TCA-related genes has yet to be fully explored.
Methods: This study began by analyzing the GSE131882 dataset to reveal the expression patterns of TCA-related genes in various renal cell types and to identify genes that differ in expression between high and low subgroups. The GSE30122 dataset was then examined to identify genes with differential expression in DN. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were applied to pinpoint TCA-related gene modules. Following this, multiple machine learning techniques were employed to analyze the TCA gene set that showed differential expression at both cellular and sample levels, allowing us to identify the hub genes. A diagnostic model was constructed, with its effectiveness validated through ROC analysis. The immune landscape of DN was assessed using ssGSEA. GeneMANIA and NetworkAnalyst were also utilized to predict genes with similar functions, as well as miRNAs and transcription factors (TFs) that may regulate these diagnostic genes. Finally, single-cell RNA sequencing (scRNA-seq) data confirmed the expression patterns of these genes.
Results: Two TCA-related genes, HPGD and G6PC, were identified as potential diagnostic markers for DN. ROC analysis demonstrated that these genes and their predictive model exhibited strong diagnostic performance in both training and validation cohorts. Immune landscape analysis revealed a more active immune microenvironment in DN patients compared to controls. Additionally, 59 miRNAs and 15 TFs were predicted to regulate the expression of HPGD and G6PC, along with 20 functionally related genes. scRNA-seq data highlighted that HPGD and G6PC are predominantly expressed in glomerular and proximal tubular cells.
Conclusion: Two reliable TCA-related biomarkers were pinpointed, potentially advancing early diagnosis and management of DN.
期刊介绍：
Acta Diabetologica is a journal that publishes reports of experimental and clinical research on diabetes mellitus and related metabolic diseases. Original contributions on biochemical, physiological, pathophysiological and clinical aspects of research on diabetes and metabolic diseases are welcome. Reports are published in the form of original articles, short communications and letters to the editor. Invited reviews and editorials are also published. A Methodology forum, which publishes contributions on methodological aspects of diabetes in vivo and in vitro, is also available. The Editor-in-chief will be pleased to consider articles describing new techniques (e.g., new transplantation methods, metabolic models), of innovative importance in the field of diabetes/metabolism. Finally, workshop reports are also welcome in Acta Diabetologica.
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