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

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

Journal Name: Current Molecular Medicine

Volume 15 , Issue 4 , 2015

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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.

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

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Article Details

VOLUME: 15
ISSUE: 4
Year: 2015
Page: [360 - 367]
Pages: 8
DOI: 10.2174/1566524015666150401102218
Price: $58

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