Discovery and validation of novel blood biomarkers of breast and prostate cancer

Identification of novel biomarkers of breast and prostate cancers to supplement current diagnostic, prognostic and predictive tools is an important clinical need. Interaction between the host’s immune system and tumours is reflected in detectable changes in profiles of proteins in blood cells and therefore these cells can be a source for cancer biomarkers. In a previous investigation conducted in our laboratory, a panel of proteins differentially expressed in white blood cells (WBCs) of patients with primary and advanced breast cancer (BRCA and ABC cohorts, respectively) was identified using integrated approaches. The aim of the present study was to assess the biomarker potential of five proteins: Serpin B1, Lipocalin 2, Copine 3, Integrin 4 and 5LOX, using Western blot, immunofluorescence, flow cytometry and ELISA techniques. Serpin B1, Lipocalin 2, 5LOX and Copine 3 were present in neutrophils, whereas Integrin 4 was detected in T-lymphocytes. Significantly higher levels of Serpin B1 and Lipocalin 2, and lower levels of Integrin 4 were observed in WBCs in the BRCA cohort compared to healthy individuals, suggesting their utility as early breast cancer biomarkers. Levels of Serpin B1 and Lipocalin 2 increased and Integrin 4 decreased as the disease advanced, indicating their utility as biomarkers of poor prognosis. Lower basal levels of Serpin B1 in patients undergoing chemotherapy and endocrine treatment correlated with complete response to treatment. Additionally, the utility of BORIS as a diagnostic marker was investigated in plasma of breast cancer patients and urinary sediments and exosomes of prostate cancer patients. The presence of BORIS autoantibodies was demonstrated in plasma of breast cancer patients. The highest levels of BORIS mRNA were detected in urine of prostate cancer patient with the advanced disease. This indicates potential of the BORIS for breast cancer diagnosis and its utility for the prediction of the aggressiveness in prostate cancer.