BackgroundWith the rapid development and wide application of high-throughput sequencing technology, biomedical research has entered the era of large-scale omics data. We aim to identify genes associated with breast cancer prognosis by integrating multi-omics data.MethodGene-gene interactions were taken into account, and we applied two differential network methods JDINAC and LGCDG to identify differential genes. The patients were divided into case and control groups according to their survival time. The TCGA and METABRIC database were used as the training and validation set respectively.ResultIn the TCGA dataset, C11orf1, OLA1, RPL31, SPDL1 and IL33 were identified to be associated with prognosis of breast cancer. In the METABRIC database, ZNF273, ZBTB37, TRIM52, TSGA10, ZNF727, TRAF2, TSPAN17, USP28 and ZNF519 were identified as hub genes. In addition, RPL31, TMEM163 and ZNF273 were screened out in both datasets. GO enrichment analysis shows that most of these hub genes were involved in zinc ion binding.ConclusionIn this study, a total of 15 hub genes associated with long-term survival of breast cancer were identified, which can promote understanding of the molecular mechanism of breast cancer and provide new insight into clinical research and treatment.