title: High Expression of Human Leukocyte Antigen-G is Associated with a Poor Prognosis in Patients with PDAC.
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.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: J
authors.initials: J
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Long
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Ni
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai 200032, China. yuxianjun@fudanpci.org.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D059951:HLA-G Antigens / Q000097:blood*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D018106:CD28 Antigens; D059951:HLA-G Antigens