Comprehensive analysis reveals potential hub genes and therapeutic drugs in an acquired lymphedema model

Abstract

Background: Acquired lymphedema is a common and often severe complication of breast cancer surgery and radiology that seriously affects patients’ quality of life. Nevertheless, the pathogenesis for acquired lymphedema is complex and remains unclear. The aim of this study is to find out possible genetic markers and potential drugs for acquired lymphedema. Methods: First, the GSE4333 datasets, which include expression data for six female humanized hairless immunocompetent SKH-1 mice (the condition of whom mimics acquired lymphedema), were reanalyzed. According to the criteria of a fold change (FC) ≥1.4 and an adjusted P value <0.05, we identified the differentially expressed genes (DEGs) between a normal group and the lymphedema group. Next, we analyzed the Gene Ontology (GO) terms and enriched signaling pathways associated with these DEGs with an online tool DAVID. We also constructed protein-protein interaction (PPI) networks and selected meaningful gene modules for additional gene-drug interaction research. Finally, the extant drugs targeting these module genes were identified for further study of their therapeutic effects against acquired lymphedema. Results: A total of 481 DEGs were identified that were closely associated with the immune system, inflammatory response, and extracellular matrix (ECM) structural constituent terms, among others. Moreover, we identified the top 10 significant genes in the PPI networks and identified one extant drug, fiboflapon, that targets the ALOX5AP gene. Conclusions: We ultimately identified 10 hub genes, molecular mechanisms, and one extant drug related to acquired lymphedema. The findings identified targets and a potential drug for further research on acquired lymphedema.