Data from Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection

Abstract

<div>Abstract<p><b>Purpose:</b> 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).</p><p><b>Experimental Design:</b> Immunohistochemical staining of HLA-G expression as well as tumor-infiltrating FoxP3<sup>+</sup> regulatory (Tregs) and CD8<sup>+</sup> 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.</p><p><b>Results:</b> HLA-G expression was associated with HCC prognosis, especially in early-stage diseases, with high expression independently associated with shortened overall survival (<i>P</i> = 0.041) and increased tumor recurrence (<i>P</i> = 0.023). HLA-G level was positively related to Tregs/CD8<sup>+</sup> 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 <i>P</i> < 0.001). In addition, HLA-G1 expression increased in a concordant manner with the increase of metastatic potential in human HCC cell lines.</p><p><b>Conclusions:</b> 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<sup>+</sup> ratio added the prognostic power to both variables, offering a possible strategy of tumor-stroma interaction-oriented cancer immunotherapy.</p></div>