Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, China.
Hum Immunol. 2010 Sep;71(9):892-8. doi: 10.1016/j.humimm.2010.06.009. Epub 2010 Jun 12.
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.
人类白细胞抗原（HLA）-G 可以抑制免疫细胞的功能，并诱导调节性 T 细胞（Treg），可能参与抗肿瘤免疫反应。在本研究中，采用免疫组织化学法分析了 58 例原发性乳腺癌病变中的 HLA-G 表达。采用酶联免疫吸附试验检测 92 例乳腺癌患者和 70 例正常健康供者的血浆可溶性 HLA-G。采用流式细胞术分析了 64 例乳腺癌患者和 23 例正常对照者的 CD4+CD25+FoxP3+Treg 比例。在 58 例乳腺癌病变中观察到 HLA-G 表达，占 70.7%（41/58）。疾病分期（I/II 期与 III/IV 期，p=0.044）和肿瘤分级（I/II 期与 III/IV 期，p=0.021）较高的病变中 HLA-G 表达更为常见。与正常对照组相比，患者的 sHLA-G 显著增加（中位数 82.19 与 9.65 U/ml，p<0.001）；sHLA-G 的受试者工作特征（ROC）曲线下面积为 0.953（95%置信区间[CI]为 0.926-0.981，p<0.001）。然而，sHLA-G 与疾病分期和肿瘤分级无关。此外，与正常对照组相比，乳腺癌患者的 CD4+CD25+FoxP3+Treg 显著增加（4.46+/-1.36%与 2.67+/-1.45%，p<0.001），且 Treg 的增加频率与 sHLA-G 水平呈强相关（R=0.582，p=0.001）。我们的研究结果表明，HLA-G 可能在乳腺癌的进展中发挥关键作用，血浆 sHLA-G 水平可能是一种有用的术前诊断生物标志物。
