Human leukocyte antigen-G polymorphism and expression in breast cancer patients

Abstract

Human leukocyte antigen-G (HLA-G) is implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate the influence of HLA-G polymorphism and expression on breast cancer. Eighty patients with breast cancer and 80 healthy individuals were included in this study. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples, and soluble HLA-G (sHLA-G) was detected by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in 73 breast cancer lesions was also analyzed by immunohistochemistry staining. The HLA-G 3'' untranslated region (UTR) 14 bp sequence insertion was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P=0.0407). Levels of sHLA-G were higher in the breast cancer group (median sHLA-G=117.2 U/mL) compared to the control group (median sHLA-G=10.1 U/mL, P<0.0001) and also presented a significant difference between the ductal carcinoma in situ and control (P<0.0001). The area under the receiver operating characteristic curve (AU-ROC) value of sHLA-G for distinguishing breast cancer from normal controls was 0.89. A similar AU-ROC value was observed for detecting metastasis from all other groups (0.89, P<0.0001), which was greater than that of the current tumor marker CA15-3 (0.54, P<0.0001). Thus, HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.