General ICU, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China.
Interdepartmental Division of Critical Care Medicine, Departments of Anesthesia and Physiology, University of Toronto, Toronto, Canada.
Bioengineered. 2021 Dec;12(1):1457-1470. doi: 10.1080/21655979.2021.1908029.
Pediatric sepsis is a great threat to death worldwide. However, the pathogenesis has not been clearly understood until now in sepsis. This study identified differentially expressed mRNAs and lncRNAs based on Gene Expression Omnibus (GEO) database. And the weighted gene co-expression network analysis (WGCNA) was performed to explore co-expression modules associated with pediatric sepsis. Then, Gene Ontology (GO), KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, mRNA‑lncRNA and mRNA‑lncRNA-pathway co-expression network analysis was conducted in selected significant module. A total of 1941 mRNAs and 225 lncRNAs were used to conduct WGCNA. And turquoise module was selected as a significant module that was associated with particular traits. The mRNAs functions associated with many vital processes were also shown by GO and KEGG pathway analysis in the turquoise module. Finally, 15 mRNAs (MAPK14, ITGAM, HK3, ALOX5, CR1, HCK, NCF4, PYGL, FLOT1, CARD6, NLRC4, SH3GLB1, PGS1, RAB31, LTB4R) and 4 lncRNAs (GSEC, NONHSAT160878.1, XR_926068.1 and RARA-AS1) were selected as hub genes in mRNA‑lncRNA-Pathway co-expression network. We identified 15 mRNAs and 4 lncRNAs as diagnostic markers, which have potential functions in pediatric sepsis. Our study provides more directions to study the molecular mechanism of pediatric sepsis.: mRNA: messenger RNA; lncRNA: long noncoding RNAs; GEO: Gene Expression Omnibus; WGCNA: weighted gene co-expression network analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; SIRS: systemic inflammatory response syndrome; TOM: topological overlap measure; BP: biological process; MF: molecular function; CC: cellular component; ROC: receiver operating characteristic curve; AUC: area under curve; MAPK14: Mitogen-activated protein kinase 14; ALI: acute lung injury; ITGAM: Integrin subunit alpha M; HK3: Hexokinase 3; LPS: lipopolysaccharide; 5-LO: 5-lipoxygenase; LTs: leukotrienes; LTB4R: leukotriene B4 receptor.
儿科脓毒症是全球范围内死亡的巨大威胁。然而，到目前为止，脓毒症的发病机制仍不清楚。本研究基于基因表达综合数据库（GEO）鉴定了差异表达的 mRNAs 和 lncRNAs。并进行加权基因共表达网络分析（WGCNA）以探索与儿科脓毒症相关的共表达模块。然后，在选定的显著模块中进行基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路、mRNA-lncRNA 和 mRNA-lncRNA 通路共表达网络分析。总共使用了 1941 个 mRNAs 和 225 个 lncRNAs 进行 WGCNA。并选择绿松石模块作为与特定特征相关的显著模块。GO 和 KEGG 通路分析还显示了与绿松石模块中许多重要过程相关的 mRNAs 功能。最后，在 mRNA-lncRNA-Pathway 共表达网络中选择了 15 个 mRNAs（MAPK14、ITGAM、HK3、ALOX5、CR1、HCK、NCF4、PYGL、FLOT1、CARD6、NLRC4、SH3GLB1、PGS1、RAB31、LTB4R）和 4 个 lncRNAs（GSEC、NONHSAT160878.1、XR_926068.1 和 RARA-AS1）作为 hub 基因。我们鉴定了 15 个 mRNAs 和 4 个 lncRNAs 作为诊断标志物，它们在儿科脓毒症中具有潜在功能。我们的研究为研究儿科脓毒症的分子机制提供了更多方向。
mRNA：信使 RNA；lncRNA：长非编码 RNA；GEO：基因表达综合数据库；WGCNA：加权基因共表达网络分析；GO：基因本体论；KEGG：京都基因与基因组百科全书；SIRS：全身炎症反应综合征；TOM：拓扑重叠度量；BP：生物过程；MF：分子功能；CC：细胞成分；ROC：接收者操作特征曲线；AUC：曲线下面积；MAPK14：丝裂原活化蛋白激酶 14；ALI：急性肺损伤；ITGAM：整合素亚单位 alpha M；HK3：己糖激酶 3；LPS：脂多糖；5-LO：5-脂氧合酶；LTs：白三烯；LTB4R：白三烯 B4 受体。
