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He X.,Sichuan Academy of Medical Science | Dong D.-D.,Sichuan Provincial Peoples Hospital | Yie S.-M.,Sichuan Academy of Medical Science | Yie S.-M.,Chengdu Bioengineering Institute for Cancer Research | And 6 more authors.
Annals of Surgical Oncology | Year: 2010

Objective: The aim of this study is to investigate clinical implications of human leukocyte antigen-G (HLA-G) expression in breast cancer. Methods: HLA-G expression in 235 primary breast cancer tissues was investigated using immunohistochemistry, and plasma soluble HLA-G (sHLA-G) was measured in 44 breast cancer patients using a specific HLA-G enzyme-linked immunosorbent assay (ELISA). Effects of estradiol/progesterone and their antagonists tamoxifen/RU486 on HLA-G expression in cultured breast cancer MCF-7 cells were determined by real-time polymerase chain reaction (PCR) and the ELISA. Alterations of HLA-G expression by the hormone treatments on subsequent allocytotoxic lymphocyte (allo-CTL) response were also examined. Results: In the study, approximately 66% of neoplasm lesions were identified to have positive HLA-G expression. This expression was significantly correlated with tumor size, nodal status, and clinical disease stage (P = 0.0001, 0.012, and 0.0001, respectively). Patients with positive HLA-G expression had a lower survival rate than those with negative expression (P < 0.028). Plasma sHLA-G levels were significantly higher in breast cancer patients than in healthy controls (P < 0.001), with the area under the receiver-operating characteristic (ROC) curve being 0.95. HLA-G expression in breast cancer MCF-7 cells was enhanced by estradiol/progesterone but reduced by their antagonists. Cytotoxicity studies showed that allo-CTL response in MCF-7 cells was inhibited by prior treatment with estradiol/progesterone, but was amplified by their antagonists. The effects could be restored or further strengthened by the addition of anti-HLA-G antibodies. Conclusion: Our findings suggest that HLA-G may have potential clinical implications in diagnosis, prognosis, and immunotherapy of patients with breast cancer. © 2010 Society of Surgical Oncology. Source


Cao M.,Sichuan Academy of Medical Science | Yie S.-M.,Sichuan Academy of Medical Science | Yie S.-M.,Chengdu University of Traditional Chinese Medicine | Yie S.-M.,Chengdu Bioengineering Institute for Cancer Research | And 4 more authors.
Tissue Antigens | Year: 2011

Human leukocyte antigen-G (HLA-G) is a novel tumor marker and its soluble isoforms produce secretory proteins. Increased soluble HLA-G (sHLA-G) levels have been reported in patients with melanoma, neuroblastoma, lymphoproliferative disorders, breast, ovarian and colorectal carcinoma when compared to healthy controls or subjects with benign neoplasms. The aim of this study is to investigate whether or not plasma sHLA-G can be used as a potential biomarker for cancer diagnosis. We measured plasma sHLA-G levels in 166 patients with early stages of colorectal cancer (CRC, n = 37), gastric cancer (GC, n = 28), esophageal squamous cell carcinoma (ESCC, n = 58) and non-small cell lung cancer (NSCLC, n = 43), and compared them to healthy controls (n = 260) by using a specific HLA-G enzyme-linked immunosorbent assay (ELISA). We found that plasma sHLA-G levels were significantly higher in cancer patients than in healthy controls (all P < 0.0001). The areas under the receiver-operating characteristic (ROC) curves for sHLA-G were 0.97, 0.91, 0.98 and 0.80 for healthy controls vs CRC, GC, ESCC and NSCLC, respectively. At 100% specificity, the highest sensitivity achieved to detect CRC, GC, ESCC and NSCLC was 94% [95% confidence interval (CI), 89-99], 85% (95% CI, 76-94), 91% (95% CI, 88-94) and 51% (95% CI, 43-59) at a cutoff value of 49 U/ml, respectively. These findings suggest that plasma sHLA-G may be a useful molecule in the differential diagnosis of these malignancies against healthy controls. © 2011 John Wiley & Sons A/S. Source

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