• Open Access

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

Authors


Correspondence to: Wei-Hua YAN, M.D., Ph.D.,
Medical Research Center, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang 317000, China.
Tel.: +86–576-8519 9347
Fax: +86–576-8519 9876
E-mail: yanwhcom@yahoo.com

Abstract

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.

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