{"title":"血液转录组分析显示循环单核细胞中CTSB和ATP6V0D1的表达是脓毒症的潜在生物标志物。","authors":"Yaojun Peng, Qiyan Wu, Baimei Zhuang, Xinhuan Ding, Yawen Peng, Di Jing, Maolin Xu, Meng Wang, Yanchao Liang, Bo Pan, Yuyu Liu, Haiyan Zhu","doi":"10.1097/SHK.0000000000002693","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a dysregulated host response to infections, leading to organ dysfunction and posing a critical threat to human health. Despite tremendous progress in understanding the pathophysiology of sepsis, early diagnosis and clinical treatment efficacy remain unsatisfactory. This study aimed to identify transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) as potential biomarkers of sepsis.</p><p><strong>Methods: </strong>Bulk RNA-seq was performed on PBMCs obtained from 20 patients with sepsis and 12 healthy individuals. Multiple bioinformatics tools were used to identify key genes and signaling pathways associated with sepsis progression. The hub genes were further externally validated by publicly available blood transcriptomic data and experimentally verified by immunocytofluorescence assay.</p><p><strong>Results: </strong>Differential expression analysis revealed 4,522 differentially expressed genes (DEGs) in patients with sepsis (n = 20) compared to healthy individuals (n = 12). Weighted gene co-expression network analysis identified multiple gene modules closely related to sepsis, with the royal blue module exhibiting the most positive correlation with sepsis. Intersection analysis yielded 176 common genes between the royal blue module genes and DEGs. Protein-protein interaction analysis revealed five hub genes (CTSB, CTSD, ATP6V0D1, UBE2D1, and ATP6V0C) associated with sepsis. Immune infiltration was dissected by single sample gene set enrichment analysis, revealing associations between hub genes and monocytes. Single-cell RNA sequencing data analysis and immunocytofluorescence assay confirmed the upregulation of CTSB and ATP6V0D1 in circulating monocytes. Notably, CTSB and ATP6V0D1 were significantly associated with 28-day mortality of sepsis patients in the external validation cohort (n = 479).</p><p><strong>Conclusion: </strong>This study identifies CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers and promising therapeutic targets for sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood transcriptome analysis reveals CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers of sepsis.\",\"authors\":\"Yaojun Peng, Qiyan Wu, Baimei Zhuang, Xinhuan Ding, Yawen Peng, Di Jing, Maolin Xu, Meng Wang, Yanchao Liang, Bo Pan, Yuyu Liu, Haiyan Zhu\",\"doi\":\"10.1097/SHK.0000000000002693\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Sepsis is a dysregulated host response to infections, leading to organ dysfunction and posing a critical threat to human health. Despite tremendous progress in understanding the pathophysiology of sepsis, early diagnosis and clinical treatment efficacy remain unsatisfactory. This study aimed to identify transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) as potential biomarkers of sepsis.</p><p><strong>Methods: </strong>Bulk RNA-seq was performed on PBMCs obtained from 20 patients with sepsis and 12 healthy individuals. Multiple bioinformatics tools were used to identify key genes and signaling pathways associated with sepsis progression. The hub genes were further externally validated by publicly available blood transcriptomic data and experimentally verified by immunocytofluorescence assay.</p><p><strong>Results: </strong>Differential expression analysis revealed 4,522 differentially expressed genes (DEGs) in patients with sepsis (n = 20) compared to healthy individuals (n = 12). Weighted gene co-expression network analysis identified multiple gene modules closely related to sepsis, with the royal blue module exhibiting the most positive correlation with sepsis. Intersection analysis yielded 176 common genes between the royal blue module genes and DEGs. Protein-protein interaction analysis revealed five hub genes (CTSB, CTSD, ATP6V0D1, UBE2D1, and ATP6V0C) associated with sepsis. Immune infiltration was dissected by single sample gene set enrichment analysis, revealing associations between hub genes and monocytes. Single-cell RNA sequencing data analysis and immunocytofluorescence assay confirmed the upregulation of CTSB and ATP6V0D1 in circulating monocytes. Notably, CTSB and ATP6V0D1 were significantly associated with 28-day mortality of sepsis patients in the external validation cohort (n = 479).</p><p><strong>Conclusion: </strong>This study identifies CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers and promising therapeutic targets for sepsis.</p>\",\"PeriodicalId\":21667,\"journal\":{\"name\":\"SHOCK\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"SHOCK\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/SHK.0000000000002693\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002693","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Blood transcriptome analysis reveals CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers of sepsis.
Background: Sepsis is a dysregulated host response to infections, leading to organ dysfunction and posing a critical threat to human health. Despite tremendous progress in understanding the pathophysiology of sepsis, early diagnosis and clinical treatment efficacy remain unsatisfactory. This study aimed to identify transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) as potential biomarkers of sepsis.
Methods: Bulk RNA-seq was performed on PBMCs obtained from 20 patients with sepsis and 12 healthy individuals. Multiple bioinformatics tools were used to identify key genes and signaling pathways associated with sepsis progression. The hub genes were further externally validated by publicly available blood transcriptomic data and experimentally verified by immunocytofluorescence assay.
Results: Differential expression analysis revealed 4,522 differentially expressed genes (DEGs) in patients with sepsis (n = 20) compared to healthy individuals (n = 12). Weighted gene co-expression network analysis identified multiple gene modules closely related to sepsis, with the royal blue module exhibiting the most positive correlation with sepsis. Intersection analysis yielded 176 common genes between the royal blue module genes and DEGs. Protein-protein interaction analysis revealed five hub genes (CTSB, CTSD, ATP6V0D1, UBE2D1, and ATP6V0C) associated with sepsis. Immune infiltration was dissected by single sample gene set enrichment analysis, revealing associations between hub genes and monocytes. Single-cell RNA sequencing data analysis and immunocytofluorescence assay confirmed the upregulation of CTSB and ATP6V0D1 in circulating monocytes. Notably, CTSB and ATP6V0D1 were significantly associated with 28-day mortality of sepsis patients in the external validation cohort (n = 479).
Conclusion: This study identifies CTSB and ATP6V0D1 expression in circulating monocytes as potential biomarkers and promising therapeutic targets for sepsis.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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