Aberrant human leucocyte antigen-G expression and its clinical relevance in hepatocellular carcinoma.
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.
Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, China.
A
A
Lin
H-X
HX
Chen
C-C
CC
Zhu
X
X
Zhang
H-H
HH
Xu
J-G
JG
Zhang
Q
Q
Wang
W-J
WJ
Zhou
W-H
WH
Yan
D000328:Adult; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D056945:Hep G2 Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D046888:Tissue Array Analysis; D014162:Transfection
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I