De novo proteins ESF1 and MIPEP promote luminal breast cancer proliferation and predict the patient’s prognosis

Abstract Background Luminal breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to address this unmet need. Method Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between luminal breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemistry (IHC) and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. Result A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in lumina breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with apoptotic and metabolic pathways. STRING analysis found ESF1 and MIPEP were the de novo hub genes in breast cancer, whose increased expressions were verified by the IHC and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression negatively correlated with patient prognosis and helped predict their immunotherapy efficacy. Conclusion The upregulation of ESF1 and MIPEP promoted luminal breast cancer proliferation, which might provide novel targets for the development of new therapies.