Exploration Of Differential HLA Polymorphism,LMP2A-specific T Cell Immune Response And Prognosis In Xinjiang Uyghur,Han Patients With Nasopharyngeal Carcinoma

Objective: Investigation of the polymorphism about human leukocyte antigen(HLA)allele, LMP2A-specific T cell Immune Response and Prognosis in Xinjiang Uyghur and Han patients with nasopharyngeal carcinoma. Methods: Seventy-two Uyghur and eighty-one Han patients with newly diagnosed NPC without other infectious and autoimmune diseases recruited at the Affiliated Tumor Hospital of Xinjiang Medical University between January 1, 2011 and December 31, 2014 were included in the study.Healthy controls were from volunteers of the students and staff in the same hospital. HLA allele frequency were compared between patients in the two ethnical groups and patients with corresponding healthy controls using DNA extractions from periphery venous blood by polymerase chain reaction/sequence specific primers(PCR-SSP). Comparative characteristics of LMP2 A specific immune response in above groups were conducted in peripheral blood mononuclear cells using ELISPOT. Follow-up tests were performed 3months after the initial test to compare changes of the specific T cell responses pre-and post-treatment. A retrospective analysis was carried out by collecting and analyzing the medical records of 121 Han and 60 Uyghur patients who had pathologically confirmed NPC and received IMRT radiotherapy treatment without distant metastasis. Results: The haplotypes of HLA allele frequency in Xinjiang Uyghur NPC patients showed difference from Han patients. The HLA-B46, C06, DQB107, DRB102 allele frequency in Uyghur NPC patients were significantly higher compared with that in Han population. In contrast,HLA-A02, A03, C01, DQB108, DQB109 allele frequency were significantly lower in Uyghur NPC patients than Han NPC(P<0.05).According to statistical analysis,HLA-C14(P=0.041) was considered as a susceptibility gene in NPC pathogenesis in Xinjiang Uyghur population.On the other hand HLA-A02, B46, C01 frequency was significantly higher in Han patient.Suggesting that HLA-A02, B46, C01 may be related to susceptibility to Han NPC patient in Xinjiang aera. In contrast, HLA-A30, B13 frequency was lower in Xinjiang Han NPC, indicating that HLA-A30, B13 may confer resistance to Han NPC. NPC patients showed significantly lower specific T cell immunity response to LMP2 A peptides compared with healthy controls(P=0.032, 0.048,0.033). Uyghur NPC patients showed significantly lower specific T cell immunity response to LMP2 A compared with Han patients(P=0.023). Comparative LMP2 A specific T cell immune response pre-and post-treatment was significant recovered in Han NPC patients 3 months post treatment(P=0.001). LMP2 A specific T cell immune response showed significant difference in age and T stage group in Uyghur NPC. In Han NPC patients, difference was showed in N stage and HLA-A02 positive group.Retrospective analysis of 181 NPC patients, which included 121 Han and 60 Uyghur, all patients 5 years DFS and OS, LC, RC, DMFS respectively: 80.2%, 67.9%, 87.9%and94.9%, 77.6%, between Uygur and Han patients showed no significant difference. Age is the common influential factor of OS, DFS in both Uighur and Han patients. Furthermore,N staging was the independent prognostic factors of NPC OS in Han and NPC DFS in Uyghur patients. Conclusion: There were individual characteristics in HLA polymorphism, T cell immune and the factors influencing prognosis in Xinjiang Uyghur and Han patients with NPC.