Abstract
BACKGROUND: Breast cancer (BC) is one of the most common cancers in women, significantly contributing to cancer-related death in the modern world. Obesity, as a worldwide epidemic besides the menopausal status, has a paradoxical association with BC. OBJECTIVES: To determine the molecular mechanisms underlying the paradoxical effects of obesity on BC, a comprehensive systems biology analysis was performed. METHODS: Data retrieval, data preprocessing, and differential expression analysis were conducted. Weighted correlation network analysis (WGCNA) identified the gene modules associated with clinical traits. Network analysis and hub gene identification techniques revealed key regulatory genes, and functional enrichment analysis uncovered biological pathways related to hub genes. A logistic regression model was developed to predict menopausal status based on hub genes. Additionally, gene expression analysis of two important genes was performed by qPCR. RESULTS: The study identified the hub genes and molecular pathways (the PI3K-Akt signaling pathway, proteoglycans in cancer, and lipid metabolic and atherosclerosis pathways) associated with the obesity paradox in BC based on menopausal statutes. CONCLUSIONS: These results may improve our understanding of the underlying mechanisms of the effects of body mass on BC and assist in identifying biomarkers and potential therapeutic targets for treating obese postmenopausal women with BC.