Analysis of mRNA‑lncRNA and mRNA‑lncRNA-pathway co‑expression networks based on WGCNA in developing pediatric sepsis

Xiaojuan Zhang; Yuqing Cui; Xianfei Ding; Shaohua Liu; Bing Han; Xiaoguang Duan; Haibo Zhang; Tongwen Sun

doi:10.1080/21655979.2021.1908029

Analysis of mRNA‑lncRNA and mRNA‑lncRNA-pathway co‑expression networks based on WGCNA in developing pediatric sepsis

Bioengineered. 2021 Dec;12(1):1457-1470. doi: 10.1080/21655979.2021.1908029.

Authors

Xiaojuan Zhang¹, Yuqing Cui¹, Xianfei Ding¹, Shaohua Liu¹, Bing Han¹, Xiaoguang Duan¹, Haibo Zhang², Tongwen Sun¹

Affiliations

¹ 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.
² Interdepartmental Division of Critical Care Medicine, Departments of Anesthesia and Physiology, University of Toronto, Toronto, Canada.

Abstract

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.Abbreviations: 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.

Keywords: Pediatric sepsis; WGCNA; diagnostic markers; lncRNA; mRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / metabolism
Child
Databases, Genetic
Gene Expression Profiling
Humans
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Messenger / genetics*
RNA, Messenger / metabolism
Sepsis / genetics
Sepsis / metabolism*
Transcriptome / genetics*

Substances

Biomarkers
RNA, Long Noncoding
RNA, Messenger

Grants and funding

This study was supported by the United Fund of National Natural Science Foundation of China (Grant No. U2004110); Leading Talents Fund in Science and Technology Innovation in Henan Province (Grant No.194200510017); Science and Technology people-benefit project of Zhengzhou (2019KJHM0001); The special fund for young and middle-aged medical research of China International Medical Exchange Foundation (Grant No. Z-2018-35); The integrated thinking research foundation of the China foundation for International Medical Exchange (Grant No. Z-2016-23-2001); The study of mechanism of Gabexate Mesilate in the treatment of sepsis and septic shock (Grant No. 2019-hx-45).