An Integrating Analysis Reveals Key Regulatory Networks in Breast Cancer

Breast cancer is the second most common cancer diagnosed with women in the United States. Treatment of the disease has been substantially improved in recent years. However, the 5-year survival rate of patients with distant metastatic breast cancer is still below 30%. The transcription factors (TFs) regulate the expression of many genes and are commonly mutated in cancer. It has been shown that targeting transcript factor activity is effective in cancer treatment. In this study, we performed a large-scale integrative analysis to reveal the TFs that play essential regulatory roles in disease development. We first constructed expression networks based on gene expression correlation patterns in normal and tumor tissues. Incorporating the Bayesian analysis, TF and target interactions and methylation analysis with the expression networks, we identified a total of 19 regulatory networks consisting of differentially expressed genes. Gene set enrichment analysis of TF targets further revealed four core regulatory networks that were mainly controlled by 10 transcription factors. The dysregulated gene networks and their major TF regulators inferred by our study provide new insights into the regulatory mechanisms of breast cancer and offer new therapeutic targets.