Upregulation of human leukocyte antigen–G expression and its clinical significance in ductal breast cancer

Abstract Human leukocyte antigen(HLA)–G could inhibit functions of immune cells and induce regulatory T cells (Treg) and could be involved in antitumor immune responses. In the current study, HLA-G expression in 58 primary breast cancer lesions was analyzed with immunohistochemistry. Plasma soluble HLA-G was detected with enzyme-linked immunosorbent assay in 92 breast cancer patients and in 70 normal healthy donors. The proportion of CD4+ CD25+ FoxP3+ Treg was analyzed with flow cytometry in 64 breast cancer patients and 23 normal controls. HLA-G expression was observed in 70.7% (41/58) of breast cancer lesions. Lesion HLA-G expression was more frequently observed in advanced disease stage (I/II vs III/IV, p = 0.044) and tumor grade (I/II vs III/IV, p = 0.021). sHLA-G was dramatically increased in patients when compared with normal controls (median 82.19 vs 9.65 U/ml, p < 0.001); The area under the receiver operating characteristic (ROC) curve for sHLA-G was 0.953 (95% confidence interval [CI] = 0.926–0.981, p < 0.001). However, sHLA-G was irrelevant to the disease stage and tumor grade. Moreover, CD4+ CD25+ FoxP3+ Treg are markedly increased in the breast cancer patients compared with normal controls (4.46±1.36% vs 2.67±1.45%, p < 0.001), and the increased frequency of Treg was strongly correlated to sHLA-G levels ( R = 0.582, p = 0.001). Our findings indicated that HLA-G could play critical roles in the progression of breast cancer, and plasma sHLA-G levels might be a useful preoperative biomarker for diagnosis.