Soluble IL-2R as a predictor of familial breast cancer

Abstract

Background: The incidence of breast cancer has been increasing annually, and breast cancer-related diseases, such as breast cancer in the young, ovarian cancer, prostate cancer, and pancreatic cancer, have clearly and steadily increased in number and have become common among the family members of patients with breast cancer. Accordingly, an increase in the incidence of familial breast cancer (FBC) is anticipated in the future. Interleukin (IL)-2 is one of the cytokines that activate cytotoxic T lymphocytes (CTLs), which are important for cancer immunity. To identify the markers of increased risk for FBC, soluble IL-2 receptor (sIL-2R) levels and immunologic factors were investigated in patients with FBC and non-familial breast cancer (NFBC).Methods: Of the 106 untreated breast cancer patients who gave consent to participate in this study, 24 had FBC and 82 had NFBC. There were 11 healthy individuals included in this study. Serum and peripheral blood mononuclear cells were collected from all patients for measurement of sIL-2R, IL-10, Vascular endothelial growth factor (VEGF), IL-17, regulatory T cells (Tregs), Myeloid derived suppressor cells (MDSCs), neutrophil to lymphocyte ratio (NLR), white blood cell (WBC) and C-reactive protein (CRP) levels. Prognosis was assessed and compared according to sIL-2R levels (low vs. high). Tissue samples from postoperative patients with high sIL-2R levels were stained with programmed cell death ligand 1 (PD-L1) and Cluster of Differentiation (CD) 8.Results: sIL-2R level was significantly higher and had significantly stronger correlation with IL-10, VEGF, IL-17, Tregs, MDSCs levels, NLR, WBC count and CRP in FBC, than in NFBC. In cases with high sIL-2R levels, Tregs and MDSCs levels were significantly higher and the overall survival (OS) and disease free survival (DFS) rates were significantly worse in FBC than in NFBC. Among the FBC cases with high sIL-2R levels, triple negative breast cancer tissues stained well for PD-L1and CD8.Conclusions: Compared with NFBC, FBC was associated with higher sIL-2R level, Th2 predominance, and less aggressive cancer immunosuppressive cells. In the present study, sIL-2R was identified as a biomarker that can predict the prognosis of FBC. The ability to prospectively identify patients who are less likely to have NFBC is a vital step in improving the overall survival of this population.