Upregulation of human leukocyte antigen-G expression and its clinical significance in ductal breast cancer.
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.
Chen
Hai-Xiao
HX
Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, China.
Lin
Aifen
A
Shen
Chao-Jun
CJ
Zhen
Rui
R
Chen
Bao-Guo
BG
Zhang
Xia
X
Cao
Fei-Ling
FL
Zhang
Jian-Gang
JG
Yan
Wei-Hua
WH
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D044584:Carcinoma, Ductal / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006680:HLA Antigens / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D012680:Sensitivity and Specificity; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I