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.

• Authors: Hai-Xiao Chen, Aifen Lin, Chao-Jun Shen, Rui Zhen, Bao-Guo Chen, Xia Zhang, Fei-Ling Cao, Jian-Gang Zhang, Wei-Hua Yan
• Journal: Human immunology (Hum Immunol) Vol. 71 Issue 9 Pg. 892-8 (Sep 2010) ISSN: 1879-1166 [Electronic] United States
• PMID: 20547193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• FOXP3 protein, human
• Forkhead Transcription Factors
• HLA Antigens
• HLA-G Antigens
• Histocompatibility Antigens Class I

Topics

• Adult
• Biomarkers (blood)
• Breast Neoplasms (blood, diagnosis, immunology, metabolism, pathology)
• Carcinoma, Ductal (blood, diagnosis, immunology, metabolism, pathology)
• Cell Count
• Cell Membrane (metabolism)
• Cytoplasm (metabolism)
• Female
• Forkhead Transcription Factors (metabolism)
• HLA Antigens (blood, immunology, metabolism)
• HLA-G Antigens
• Histocompatibility Antigens Class I (blood, immunology, metabolism)
• Humans
• Middle Aged
• Neoplasm Staging
• ROC Curve
• Sensitivity and Specificity
• T-Lymphocytes, Regulatory (metabolism, pathology)
• Up-Regulation