Evaluating plasma antibody repertoires in breast cancer patients with progesterone receptor positive and negative tumors

Abstract

Abstract Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Early cancer detection and tumors molecular characterization are the key measures for effective therapy. Molecular changes associated with tumor development are detected by the immune system and reflected with specific antibody production. We used microarrays containing 120K of peptides with random amino acid sequences to analyze the repertoire of circulating antibodies in the blood plasma of patients with early stages of breast cancer (BC). Previously we have shown that healthy donors and BC patients have distinct circulating antibody repertoires. Further analysis reviled that BC patients with various progesterone receptor (PR) expression levels also have circulating antibodies reacting with different peptides (mimotopes) on microarrays. In this study we selected 61 peptides from 120K peptides presented on microarrays that show statistically significant difference for the interaction with the circulating antibodies of blood plasma from PR+ and PR- BC patients. Peptides interacting with PR+ and PR- patients plasma have common amino acid motifs suggesting that patients with tumors expressing different PR levels mount specific immune response reflecting molecular changes associated with various tumor subtype. Therefore, the panel of peptides that specifically interact with the immunoglobulins of patients with different PR expression can be used for the development of non-invasive test systems. Thus, peptide microarrays can be used to create a new tool for studying the repertoire of circulating antibodies for different diseases evaluation. Supported by grant FZMW-2020-0007. Supported by grants from the Ministry of Science and Higher Education of the Russian Federation (FZMW-2020-0007)