Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection
Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection
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DOI：
10.1158/1078-0432.ccr-09-0463
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发表时间：
2009-07-15
影响因子：
11.5
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Cai, Ming-Yan;Xu, Yong-Feng;Fan, Jia
目的：人类白细胞抗原-G(人类白细胞抗原-G)是一种参与肿瘤逃逸机制的肿瘤相关免疫抑制分子。本研究的目的是阐明其在肝细胞癌中的预后意义。实验设计：在包含173个肝细胞癌组织标本的组织芯片上，进行了人类白细胞抗原-G的表达以及肿瘤浸润性FoxP3(+)调节性T细胞(Tregs)和CD8(+)细胞毒性T细胞的免疫组织化学染色。结果：HL A-G的表达与肝细胞癌的预后有关，特别是在早期病变中，高表达与总生存期缩短(P=0.041)和肿瘤复发增加(P=0.023)独立相关。HL A-G水平与T细胞亚群/CD_8(+)比值呈正相关，两者同时高水平的患者死亡和肿瘤复发的风险是合并低水平患者的3倍以上(P均<0.001)。结论：HLAG蛋白在肝细胞癌中的过度表达是预后不良的独立指标，尤其是在早期病变中。人类白细胞抗原-G的表达和Tregs/CD8(+)比值的结合增加了这两个变量的预后能力，为肿瘤-间质相互作用的癌症免疫治疗提供了一种可能的策略。
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.