{"title":"IDENTIFICATION AND VERIFICATION OF FEATURE BIOMARKERS ASSOCIATED WITH CHOLINE METABOLISM IN SEPSIS-INDUCED CARDIOMYOPATHY.","authors":"Meng-Qin Pei, Zhen-Dong Sun, Yu-Shen Yang, Yu-Ming Fang, Ya-Fen Zeng, He-Fan He","doi":"10.1097/SHK.0000000000002513","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Background: Sepsis-induced cardiomyopathy ( SIC ), one of the most common complications of sepsis, seriously affects the prognosis of critically ill patients. Choline metabolism is an important biological process in the organism, and the mechanism of its interaction with SIC is unclear. The aim of this study was to reveal the choline metabolism genes (CMGs) associated with SIC and to provide effective targets for the treatment of SIC . Methods: Through a comprehensive analysis of the microarray dataset GSE79962 (comprising 20 SIC patients and 11 healthy controls) from the GEO database, suspected co-expression modules and differentially expressed genes (DEGs) in SIC were identified. Hub CMGs were obtained by intersecting choline metabolism database with DEGs and key model genes. Afterward, hub CMGs most significantly involved in prognosis were further analyzed for the verification of major pathways of enrichment analysis. Finally, the expression of hub CMGs in in vivo and in vitro SIC model was verified by immunohistochemistry staining and quantitative real-time polymerase chain reaction analysis (qPCR). Results: Weighted gene co-expression network analysis identified 1 hub gene panel and 3,867 hub genes, which were intersected with DEGs and CMGs to obtain the same 3 hub CMGs:HIF-1α, DGKD, and PIK3R1. Only HIF-1α shows significant association with mortality ( P = 0.009). Subsequent differential analysis based on the high and low HIF-1α expression yielded 63 DEGs and then they were uploaded into Cytoscape software to construct a protein-protein interaction network and 6 hub genes with the highest priority were obtained (CISH, THBS1, IMP1, MYC, SOCS3, and VCAN). Finally, a multifactorial COX analysis revealed a significant correlation between HIF-1α and survival in SIC patients, which was further validated by in vitro and in vivo experiments. Conclusion: Our findings will provide new insights into the pathogenesis of SIC , and HIF-1α may have important applications as a potential biomarker for early detection and therapeutic intervention in SIC .</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"456-465"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-01","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.0000000000002513","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Background: Sepsis-induced cardiomyopathy ( SIC ), one of the most common complications of sepsis, seriously affects the prognosis of critically ill patients. Choline metabolism is an important biological process in the organism, and the mechanism of its interaction with SIC is unclear. The aim of this study was to reveal the choline metabolism genes (CMGs) associated with SIC and to provide effective targets for the treatment of SIC . Methods: Through a comprehensive analysis of the microarray dataset GSE79962 (comprising 20 SIC patients and 11 healthy controls) from the GEO database, suspected co-expression modules and differentially expressed genes (DEGs) in SIC were identified. Hub CMGs were obtained by intersecting choline metabolism database with DEGs and key model genes. Afterward, hub CMGs most significantly involved in prognosis were further analyzed for the verification of major pathways of enrichment analysis. Finally, the expression of hub CMGs in in vivo and in vitro SIC model was verified by immunohistochemistry staining and quantitative real-time polymerase chain reaction analysis (qPCR). Results: Weighted gene co-expression network analysis identified 1 hub gene panel and 3,867 hub genes, which were intersected with DEGs and CMGs to obtain the same 3 hub CMGs:HIF-1α, DGKD, and PIK3R1. Only HIF-1α shows significant association with mortality ( P = 0.009). Subsequent differential analysis based on the high and low HIF-1α expression yielded 63 DEGs and then they were uploaded into Cytoscape software to construct a protein-protein interaction network and 6 hub genes with the highest priority were obtained (CISH, THBS1, IMP1, MYC, SOCS3, and VCAN). Finally, a multifactorial COX analysis revealed a significant correlation between HIF-1α and survival in SIC patients, which was further validated by in vitro and in vivo experiments. Conclusion: Our findings will provide new insights into the pathogenesis of SIC , and HIF-1α may have important applications as a potential biomarker for early detection and therapeutic intervention in SIC .
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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