IgG based immunome analyses of breast cancer patients reveal underlying signaling pathways

Background: Breast cancer is the most frequent and one of the most fatal malignancies among women. Within the concept of personalized medicine, molecular characterization of tumors is usually performed by analyzing somatic mutations, RNA gene expression signatures or the proteome by mass-spectrometry. Alternatively, the immunological fingerprint of the patients can be analyzed by protein microarrays, which is able to provide another layer of molecular pathological information without invasive intervention. Results: We have investigated the immune signature of breast cancer patients and compared them with healthy controls, using protein microarray-based IgG profiling. The identified differentially reactive antigens (n=517) were further evaluated by means of various pathway analysis tools. Our results indicate that the immune signature of breast cancer patients shows a clear distinction from healthy individuals characterized by differentially reactive antigens involved in known disease relevant signaling pathways, such as VEGF, AKT/PI3K/mTOR or c-KIT, which is in close agreement with the findings from RNA-based expression profiles. Conclusion: Differential antigenic properties between breast cancer patients and healthy individual classes can be defined by serum-IgG profiling on protein microarrays. These immunome profiles provide an additional layer of molecular pathological information, which has the potential to refine and complete the systems biological map of neoplastic disease.