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

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

2020Frontiers in Genetics18 citationsDOIOpen Access PDF

Abstract

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 and 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: MMP25, MMP9, SIRPA, CKAP4, SLCO4C1, and SLC2A3; 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: LEF1, ITK, CD6, RASGRP1, IL7R, SKAP1, CD3E, and ICOS. 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.

Topics & Concepts

KEGGGene co-expression networkGeneComputational biologyBiologyMMP9Microarray analysis techniquesGene regulatory networkMicroarrayGeneticsGene expressionBioinformaticsGene ontologyDownregulation and upregulationNeonatal Respiratory Health ResearchEpigenetics and DNA MethylationCongenital Diaphragmatic Hernia Studies