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批量 RNA 测序与整合单细胞 RNA 测序鉴定 BCL2A1 为脓毒症潜在的诊断和预后生物标志物。

Bulk RNA Sequencing With Integrated Single-Cell RNA Sequencing Identifies BCL2A1 as a Potential Diagnostic and Prognostic Biomarker for Sepsis.

机构信息

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Department of Disease Prevention and Control, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Public Health. 2022 Jun 27;10:937303. doi: 10.3389/fpubh.2022.937303. eCollection 2022.

Abstract

BACKGROUND

Sepsis is one of the leading causes of morbidity and mortality worldwide in the intensive care unit (ICU). The prognosis of the disease strongly depends on rapid diagnosis and appropriate treatment. Thus, some new and accurate sepsis-related biomarkers are pressing needed and their efficiency should be carefully demonstrated.

METHODS

Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to detect sepsis and monocyte/macrophage-related genes. Least absolute shrinkage and selection operator (LASSO) and random forest regression analyses were used in combination to screen out prognostic genes. Single-cell RNA sequence profiling was utilized to further verify the expression of these genes on a single cell level. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were also applied to verify the diagnostic value of the target biomarkers.

RESULTS

The intersections of the genes detected by differential expression and WGCNA analyses identified 141 overlapping candidate genes that were closely related to sepsis and macrophages. The LASSO and random forest regression analyses further screened out 17 prognostic genes. Single-cell RNA sequencing analysis detected that and might be potential biomarkers for sepsis diagnosis and the diagnostic efficacy of was further validated by ROC curve and DCA.

CONCLUSIONS

It was revealed that had good diagnostic and prognostic value for sepsis, and that it can be applied as a potential and novel biomarker for the management of the disease.

摘要

背景

脓毒症是重症监护病房(ICU)全球发病率和死亡率的主要原因之一。疾病的预后强烈依赖于快速诊断和适当的治疗。因此,迫切需要一些新的、准确的与脓毒症相关的生物标志物,并且需要仔细证明它们的效率。

方法

应用差异表达分析和加权基因共表达网络分析(WGCNA)来检测脓毒症和单核细胞/巨噬细胞相关基因。最小绝对收缩和选择算子(LASSO)和随机森林回归分析相结合,筛选出预后基因。单细胞 RNA 序列分析用于在单细胞水平上进一步验证这些基因的表达。还应用接收者操作特征(ROC)曲线和决策曲线分析(DCA)来验证目标生物标志物的诊断价值。

结果

差异表达和 WGCNA 分析检测到的基因的交集确定了 141 个与脓毒症和巨噬细胞密切相关的重叠候选基因。LASSO 和随机森林回归分析进一步筛选出 17 个预后基因。单细胞 RNA 测序分析表明,和 可能是脓毒症诊断的潜在生物标志物,并且通过 ROC 曲线和 DCA 进一步验证了 的诊断效果。

结论

研究表明, 对脓毒症具有良好的诊断和预后价值,可作为该疾病管理的潜在新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6c/9272057/469fd33899eb/fpubh-10-937303-g0001.jpg

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