A gene co-expression network-based analysis of mesenchymal stromal cells reveals novel genes and molecular pathways underlying heterotopic ossification

Abstract

BackgroundHeterotopic ossification (HO) represents a frequently seen refractory disease second to musculoskeletal injury, in which bone tissue ectopically exists within soft tissue, resulting in serious extremity loss-of-function. This work focused on identifying regulating factors and gene network associated with HO pathology. Material and MethodsWe randomized the heterotopic ossification dataset GSE94683 as HO and NON-HO group. Weighted gene co-expression network analysis (WGCNA) was applied in identifying HO related modules. We discovered differentially expressed genes (DEGs) between the two groups. Then, we integrated protein-protein interaction (PPI) network, co-expression network, enrichment analysis, gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) for identifying the HO-related pathways. We also employed GSE126118 test set to investigate hub genes related to HO. Eventually, potential therapeutics for reversing abnormal hub gene levels were predict by DGIdb. ResultsWe discovered twelve HO status modules and 1,483 DEGs in HO samples compared with NON-HO counterparts. Four hub genes were obtained from the overlap of HO related PPI and coexpression networks. Training and test sets were adopted for verification, and three abnormally high hub gene expression in HO were obtained. Functional enrichment of DEGs indicated that these genes were involved in the stem cell pluripotency regulatory pathways, cytokine-cytokine receptor interaction, as well as rap1 pathway. Based on the results from GSEA and GSVA, many hub gene sets were mainly enriched in immune responses. ConclusionWe identified a gene coexpression network associated with regulatory factors in HO, which provided a new perspective on the pathogenesis and provided potential biomarkers or therapeutic targets.