High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC

Title:High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC

Volume: 15 Issue: 4

Author(s): Y.-F. Xu, Y. Lu, H. Cheng, J. Jiang, J. Xu, J. Long, L. Liu, Q. Ni, C. Liu and X.-J. Yu

Affiliation:

Keywords: HLA-G, overall survival, pancreatic ductal adenocarcinoma (PDAC), prognosis, immune escape.

Abstract: Pancreatic Adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide. A variety of mechanisms are involved in PDAC biological behaviors, of which, the mechanisms of immune escape may be a pivotal hallmark. HLA-G is a tolerant molecule implicated in tumor escape and serves as a prognostic biomarker in tumors. Our study evaluated the expression of HLA-G in PDAC and explored its clinical significance. In a cohort of 122 PDAC patients, 78 patents (63.9%) exhibited high level of HLA-G tumor tissues. Multivariate analysis suggested that HLA-G level was an independent predictor for OS (HR = 3.894, 95% CI = 2.380-6.370, p <0.001). High level of HLA-G significantly correlated with PDAC aggressive features, such as more advanced stage (TNM Stage II) (p<0.001), extrapancreatic infiltration (T3 stage) (p<0.001), lymph node involvement (p=0.019) and poor differentiation (p=0.010). In western blot analysis, almost all of the tumor cell lines (5/6) expressed high levels of HLA-G. In ELISA analysis, the level of plasma sHLA-G in PDAC patients were significantly increased than in healthy control (P=0.0037). Further analysis revealed the level of sHLA-G inversely related to numbers of peripheral activated T cells (CD8+CD28+ T cells), which may indicate that sHLA-G inactivates T cell responses resulting in tumor immune escape. In conclusion, tumor-derived HLA-G may indicate the mechanism of immune escape and impaired PDAC clinical outcome, especially in early-stage patients, which may also be a potential therapeutic target.

Cite this article as:

Xu Y.-F., Lu Y., Cheng H., Jiang J., Xu J., Long J., Liu L., Ni Q., Liu C. and Yu X.-J., High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC, Current Molecular Medicine 2015; 15 (4) . https://dx.doi.org/10.2174/1566524015666150401102218