Identification of Potential Biomarkers of Septic Shock Based on Pathway and Transcriptome Analyses of Immune-Related Genes.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY Genetics research Pub Date : 2023-01-01 DOI:10.1155/2023/9991613
Jie Wang, Jie Cai, Linlin Yue, Xixi Zhou, Chunlin Hu, Hongquan Zhu
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Abstract

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

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基于免疫相关基因通路和转录组分析鉴定脓毒性休克的潜在生物标志物。
免疫调节对感染性休克(SS)至关重要,但尚未得到明确解释。我们的目的是通过免疫相关基因的通路和转录分析来探索SS的潜在生物标志物,以提高早期发现。利用GSE57065和GSE95233微阵列数据筛选SS中的差异表达基因(differential expression genes, DEGs),对DEGs进行Gene Ontology和KEGG (Kyoto Encyclopedia of genes and Genomes)途径富集分析,并分析免疫细胞与途径富集评分之间的相关性。采用受试者工作特征(ROC)曲线评价候选基因的预测价值。使用GSE66099、GSE4607和GSE13904数据集进行外部验证。收集6例患者和6例对照者的血液样本,通过qRT-PCR和western blotting进行验证。共鉴定出SS中550个deg;这些基因与免疫反应、炎症和感染有关。免疫相关通路及CD4 + TCM、CD8 + T细胞和前脂肪细胞的浸润水平在SS病例和对照组之间存在差异。17个基因被鉴定为SS的潜在生物标志物(ROC曲线下面积>0.9)。实验证实了SS中CD8A、CD247、CD3G、LCK和HLA-DRA的下调。我们在SS中发现了几个免疫相关的生物标志物,这些生物标志物可能会提高疾病风险的早期识别。
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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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