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构建一个用于儿科脓毒症诊断的 10 基因核心基因panel。

Constructing a 10-core genes panel for diagnosis of pediatric sepsis.

机构信息

Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

J Clin Lab Anal. 2021 Mar;35(3):e23680. doi: 10.1002/jcla.23680. Epub 2020 Dec 3.

Abstract

BACKGROUND

The lack of sensitivity and specificity of most biomarkers or the lack of relevant studies to demonstrate their effectiveness in sepsis.

METHODS

Downloaded three sets of sepsis expression data (GSE13904, GSE25504, GSE26440) from GEO. Then, using the R limma package and WGCNA analysis tocore genes. Finally, the value of these core genes was confirmed by clinical samples.

RESULTS

Compared to normal samples, we obtain many abnormally expressed genes in the pediatric sepsis. WGCNA co-expression analysis showed that genes from blue and turquoise module were close correlation with pediatric sepsis. The top 20 genes (TIMP2, FLOT1, HCK, NCF4, SERPINA1, IL17RA, PGD, PRKCD, GLT1D1, ALOX5, SIRPA, DOK3, ITGAM, S100A11, ZNF438, PLIN3, LTB4R, TSPO, MAPK14, GAS7) of the blue module of pediatric sepsis were mainly enriched in neutrophil degranulation, etc The top 20 genes (TBC1D4, NOL11, NLRC3, ZNF121, DYRK2, ABCE1, MAGEH1, TMEM263, MCUB, MALT1, DDHD2, TRAC, NOC3L, LCK, TRMT61B, ZNF260, ENOPH1, LOC93622, NAE1, TRBC1) for turquoise module were mainly enriched in rRNA-containing ribonucleoprotein complexes exported from the nucleus, etc The selected hub gene of pediatric sepsis was combined with the markers of cell surface and found 10 core genes (HCK, PRKCD, SIRPA, DOK3, ITGAM, LTB4R, MAPK14, MALT1, NLRC3, LCK). ROC showed that AUC of the 10 core genes for diagnosis of pediatric sepsis was above 0.9.

CONCLUSION

There were many abnormally expressed genes in patients with pediatric sepsis. The panel constructed by the 10 core genes was expected to become a biomarker panel for clinical application of pediatric sepsis.

摘要

背景

大多数生物标志物的敏感性和特异性不足,或者缺乏相关研究来证明其在脓毒症中的有效性。

方法

从 GEO 下载三组脓毒症表达数据(GSE13904、GSE25504、GSE26440)。然后,使用 R limma 包和 WGCNA 分析来筛选核心基因。最后,通过临床样本验证这些核心基因的价值。

结果

与正常样本相比,我们在儿科脓毒症中获得了许多异常表达的基因。WGCNA 共表达分析表明,来自蓝色和绿松石模块的基因与儿科脓毒症密切相关。儿科脓毒症蓝色模块的前 20 个基因(TIMP2、FLOT1、HCK、NCF4、SERPINA1、IL17RA、PGD、PRKCD、GLT1D1、ALOX5、SIRPA、DOK3、ITGAM、S100A11、ZNF438、PLIN3、LTB4R、TSPO、MAPK14、GAS7)主要富集于中性粒细胞脱颗粒等过程;前 20 个基因(TBC1D4、NOL11、NLRC3、ZNF121、DYRK2、ABCE1、MAGEH1、TMEM263、MCUB、MALT1、DDHD2、TRAC、NOC3L、LCK、TRMT61B、ZNF260、ENOPH1、LOC93622、NAE1、TRBC1)主要富集于核输出的含 rRNA 的核糖核蛋白复合物等过程。选择儿科脓毒症的枢纽基因与细胞表面标志物相结合,发现了 10 个核心基因(HCK、PRKCD、SIRPA、DOK3、ITGAM、LTB4R、MAPK14、MALT1、NLRC3、LCK)。ROC 显示,这 10 个核心基因诊断儿科脓毒症的 AUC 均大于 0.9。

结论

儿科脓毒症患者存在许多异常表达的基因。由这 10 个核心基因构建的panel 有望成为儿科脓毒症临床应用的生物标志物panel。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ba9/7958006/ef3629b81d7a/JCLA-35-e23680-g012.jpg

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