AUTHOR=Cai Yao , Ma Fei , Qu LiuHong , Liu Binqing , Xiong Hui , Ma Yanmei , Li Sitao , Hao Hu 

TITLE=Weighted Gene Co-expression Network Analysis of Key Biomarkers Associated With Bronchopulmonary Dysplasia

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.539292

DOI=10.3389/fgene.2020.539292

ISSN=1664-8021

ABSTRACT=<p>Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from interactions between genes and the environment. The accurate molecular etiology of BPD remains largely unclear. This study aimed to identify key BPD-associated genes and pathways functionally enriched using weighted gene co-expression network analysis (WGCNA). We analyzed microarray data of 62 pre-term patients with BPD and 38 pre-term patients without BPD from Gene Expression Omnibus (GEO). WGCNA was used to construct a gene expression network, and genes were classified into definite modules. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of BPD-related hub genes were performed. Firstly, we constructed a weighted gene co-expression network, and genes were divided into 10 modules. Among the modules, the yellow module was related to BPD progression and severity and included the following hub genes: <italic>MMP25</italic>, <italic>MMP9</italic>, <italic>SIRPA</italic>, <italic>CKAP4</italic>, <italic>SLCO4C1</italic>, and <italic>SLC2A3</italic>; and the red module included some co-expression molecules that displayed a continuous decline in expression with BPD progression and included the following hub genes: <italic>LEF1</italic>, <italic>ITK</italic>, <italic>CD6</italic>, <italic>RASGRP1</italic>, <italic>IL7R</italic>, <italic>SKAP1</italic>, <italic>CD3E</italic>, and <italic>ICOS</italic>. GO and KEGG analyses showed that high expression of inflammatory response-related genes and low expression of T cell receptor activation-related genes are significantly correlated with BPD progression. The present WGCNA-based study thus provides an overall perspective of BPD and lays the foundation for identifying potential pathways and hub genes that contribute to the development of BPD.</p>