Aberrant human leucocyte antigen-G expression and its clinical relevance in hepatocellular carcinoma

作者:Lin A; Chen H X; Zhu C C; Zhang X; Xu H H; Zhang J G; Wang Q; Zhou W J; Yan W H*
来源:JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14(8): 2162-2171.
DOI:10.1111/j.1582-4934.2009.00917.x

摘要

The clinical relevance of human leucocyte antigen-G (HLA-G) has been postulated in malignancies. Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality worldwide; however, potential roles of HLA-G in HCC remain unknown. In the current study, HLA-G expression in 219 primary HCC lesions and their adjacent non-tumourous samples was analysed with immunohistochemistry. Correlations among HLA-G expression and various clinical parameters were evaluated. Meanwhile, functional analysis of transfected cell surface HLA-G expression on NK cell cytolysis was performed in vitro. HLA-G expression was observed in 50.2% (110/219) of primary HCC lesions, and undetectable in corresponding adjacent normal liver tissues. HLA-G expression was found in 37.8%, 41.9% and 71.4% of stage I, II and III HCC lesions, respectively. Data revealed that HLA-G expression in HCC was strongly correlated to advanced disease stage (I versus II, P = 0.882; I versus III, P = 0.020; II versus III, P = 0.037). HLA-G expression was also more frequently observed in elder patients (>= median 52 years, 57.5% versus 43.4%, P = 0.004). Meanwhile, plasma soluble HLA-G in HCC patients was significantly higher than that in normal controls (median, 92.49U/ml versus 9.29U/ml, P = 0.000). Functional assay showed that HLA-G expression in transfected cells could dramatically decrease the NK cell cytolysis (P = 0.036), which could be markedly restored by the blockade of HLA-G (P = 0.004) and its receptor ILT2 (P = 0.019). Our finding indicated that HLA-G expression was strongly correlated to advanced disease stage, and more frequently observed in elder patients. Its relevance to HCC progression might be result from the inhibition of NK cell cytolysis.