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

Constructing a 10-core genes panel for diagnosis of pediatric sepsis.
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构建用于诊断小儿脓毒症的 10 核心基因组

DOI:
10.1002/jcla.23680
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发表时间:
2021-03
影响因子:
2.7
通讯作者:
Pan J
Pan J
中科院分区:
医学4区
文献类型:
--
作者:
Zhou X;Wang Y;Chen J;Pan J

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大多数生物标志物缺乏敏感性和特异性,或者缺乏相关研究来证明它们在脓毒症中的有效性。从GEO下载了三套脓毒症表达数据(GSE13904、GSE25504、GSE26440)。然后,使用R LIMMA软件包和WGCNA对核心基因进行分析。最后,通过临床样本验证了这些核心基因的价值。与正常样本相比,我们获得了许多在儿童脓毒症中异常表达的基因。WGCNA共表达分析表明,蓝色和绿松石模块基因与儿童脓毒症密切相关。儿科败血症蓝色模块前20个基因(TIMP2、FLOT1、HCK、NCF4、SERPINA1、IL17RA、PGD、PRKCD、GLT1D1、ALOX5、Sirpa、DOK3、ITGAM、S100A11、ZNF438、PLIN3、LTB4R、TSPO、MAPK14、Gas7)主要集中在中性粒细胞脱颗粒中,而含有核外核蛋白复合体的前20个基因(TBC1D4、NOL11、NLRC3、ZNF121、DYRK2、ABCE1、GEH1、TMEM263、MCT1、MALDD2、TRAC、NOC3L、LCK、TRMT61B、ZNF260、EPHNO1、LOC93622、NAE1、RBC1)主要集中在核糖核蛋白复合体中。等筛选出的脓毒症HUB基因与细胞表面标记相结合,发现10个核心基因(HCK、PRKCD、Sirpa、DOK3、ITGAM、LTB4R、MAPK14、MALT1、NLRC3、LCK)。ROC结果显示,诊断小儿脓毒症的10个核心基因的AUC均在0.9以上。在儿童脓毒症患者中有许多基因表达异常。由10个核心基因构建的筛选板有望成为儿科败血症临床应用的生物标志物筛选板。10个核心基因组合对儿童败血症诊断的AUC值为0.936。
The lack of sensitivity and specificity of most biomarkers or the lack of relevant studies to demonstrate their effectiveness in sepsis. 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. 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. 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. The AUC of 10 core genes panel was 0.936 in diagnosis of pediatric sepsis.
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