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

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.

Graphical abstract

KEYWORDS:

• Pediatric sepsis
• mRNA
• lncRNA
• WGCNA; diagnostic markers

Highlights

1. Turquoise module is significantly correlated with pediatric sepsis.

2. The module co-expression network is enriched with inflammatory signal pathways.

3. Fifteen mRNAs and four lncRNAs are identified to be potential diagnostic markers for pediatric sepsis.

Disclosure statement

The authors declare that they have no competing interests.

Availability of data and materials

The datasets during the current study are available in the GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13904. Links to repositories for the annotation, visualization and integrated discovery are available at DAVID: http://david.abcc.ncifcrf.gov/.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

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).

Notes on contributors

Tongwen Sun

Zhang XJ and Cui YQ participated in designing the study and drafting the manuscript. Sun TW and Zhang HB designed the study, wrote and revised the manuscript. All authors contributed to and approved the final version of the manuscript.