Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection
Open Access
- 15 July 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 15 (14), 4686-4693
- https://doi.org/10.1158/1078-0432.ccr-09-0463
Abstract
Purpose: Human leukocyte antigen-G (HLA-G) is a tumor-associated immunosuppressive molecule involved in tumor escape mechanisms. The aim of this study is to elucidate its prognostic significance in hepatocellular carcinoma (HCC). Experimental Design: Immunohistochemical staining of HLA-G expression as well as tumor-infiltrating FoxP3+ regulatory (Tregs) and CD8+ cytotoxic T cells was carried out on tissue microarrays containing 173 HCC tissue specimens. Membrane-bound HLA-G1 protein expression in five human HCC cell lines was detected by Western blot. Results: HLA-G expression was associated with HCC prognosis, especially in early-stage diseases, with high expression independently associated with shortened overall survival (P = 0.041) and increased tumor recurrence (P = 0.023). HLA-G level was positively related to Tregs/CD8+ ratio and their combination served as a better prognosticator, patients having concurrent high levels of both variables at more than three times of risk of death and tumor relapse than those with concurrent low levels (both P < 0.001). In addition, HLA-G1 expression increased in a concordant manner with the increase of metastatic potential in human HCC cell lines. Conclusions: Overexpression of HLA-G protein in HCC was an independent indicator for poor outcome especially in early-stage disease. The combination of HLA-G expression and Tregs/CD8+ ratio added the prognostic power to both variables, offering a possible strategy of tumor-stroma interaction-oriented cancer immunotherapy.Keywords
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This publication has 44 references indexed in Scilit:
- Gene Expression in Fixed Tissues and Outcome in Hepatocellular CarcinomaNew England Journal of Medicine, 2008
- Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resectionZeitschrift für Krebsforschung und Klinische Onkologie, 2008
- Molecular mechanisms of hepatocellular carcinomaHepatology, 2008
- Expression and regulation of non‐classical HLA‐G in renal cell carcinomaTissue Antigens, 2008
- Expression of Human Leukocyte Antigen G (HLA-G) Correlates with Poor Prognosis in Gastric CarcinomaAnnals of Surgical Oncology, 2007
- Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 casesBreast Cancer Research and Treatment, 2007
- Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancerLaboratory Investigation, 2007
- Trogocytosis-based generation of suppressive NK cellsThe EMBO Journal, 2007
- Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristicsZeitschrift für Krebsforschung und Klinische Onkologie, 2004
- Differential in vivo and in vitro HLA-G expression in melanoma cells: potential mechanismsHuman Immunology, 2003