新疆维吾尔、汉族鼻咽癌患者HLA基因多态性、LMP2A特异性T细胞免疫应答及预后差异性研究

发布时间：2019-01-02 08:12

【摘要】：目的:分析新疆维吾尔、汉族鼻咽癌患者HLA等位基因多态性、LMP2A特异性T细胞免疫反应、预后及影响因素的差异。方法:收集新疆肿瘤医院2011年1月~2014年12月的初治鼻咽癌患者外周血标本,提取DNA,PCR-SSP法检测HLA等位基因;分离外周血单个核细胞,ELISPOT法检测治疗前及治疗结束后3个月LMP2A特异性T细胞免疫反应;回顾分析181例初治行IMRT治疗的鼻咽癌患者临床资料,分析预后及其影响因素。结果:新疆维吾尔、汉族鼻咽癌患者HLA等位基因分布及频率存在差异,维吾尔族鼻咽癌患者HLA-B46、C06、DQB107、DRB102等位基因频率高于汉族患者(P0.05);维吾尔族鼻咽癌患者HLA-A02、A03、C01、DQB108、DQB109等位基因的频率低于汉族患者(P0.05);维吾尔族鼻咽癌的易感基因为HLA-C14(P=0.041);汉族鼻咽癌的易感基因为:HLA-A02、B46、C01;保护基因为:HLA-A30、B13。初治患者LMP2A特异性T细胞免疫应答明显低于健康对照;维吾尔族患者在不同年龄、T分期组特异性T细胞反应有差异,汉族患者在不同N分期、HLA-A02等位基因携带组特异性T细胞反应有差异。治疗结束后3个月汉族患者特异性T细胞反应明显恢复。回顾分析181例鼻咽癌初治患者,其中维吾尔族60例,汉族121例,全组患者5年OS、DFS、LC、RC、DMFS分别为:80.2%、67.9%、87.9%、94.9%、77.6%,维吾尔族和汉族患者之间无差异。维吾尔族患者OS的影响因素为:年龄;DFS的影响因素为:年龄、N分期;汉族患者OS的影响因素为:年龄、N分期;DFS的影响因素为:年龄。维吾尔族患者放射治疗引起的皮肤、粘膜反应轻于汉族患者。结论:新疆维吾尔族和汉族鼻咽癌患者在遗传、T细胞免疫、预后影响因素方面存在差异。
[Abstract]:Objective: to analyze the difference of HLA allele polymorphism, LMP2A specific T cell immune response, prognosis and influencing factors in patients with nasopharyngeal carcinoma (NPC) in Xinjiang Uygur and Han nationality. Methods: the peripheral blood samples of nasopharyngeal carcinoma patients from January 2011 to December 2014 in Xinjiang Cancer Hospital were collected and HLA alleles were detected by DNA,PCR-SSP method. Peripheral blood mononuclear cells (PBMC) were isolated and LMP2A specific T cell immunoreaction was detected by ELISPOT method before and 3 months after treatment. Clinical data of 181 patients with nasopharyngeal carcinoma treated with IMRT were analyzed retrospectively and the prognosis and its influencing factors were analyzed. Results: the distribution and frequency of HLA allele in Xinjiang Uygur and Han nationality patients were different. The frequency of HLA-B46,C06,DQB107,DRB102 allele in Uygur nasopharyngeal carcinoma patients was higher than that in Han nationality patients (P0.05). The frequency of HLA-A02,A03,C01,DQB108,DQB109 allele in patients with nasopharyngeal carcinoma of Uygur nationality was lower than that in Han nationality (P0.05), and the susceptible base of nasopharyngeal carcinoma in Uygur nationality was HLA-C14 (P0. 041). The susceptibility gene of nasopharyngeal carcinoma in Han nationality is: HLA-A02,B46,C01; protection gene: HLA-A30,B13. The immune response of LMP2A specific T cells in the newly treated patients was significantly lower than that in the healthy controls. The specific T cell response of Uygur patients at different age and T stage group was different, while that of Han nationality patients was different at different N stages. The specific T cell response of HLA-A02 allele carrying group was different. The specific T cell response of Han nationality patients recovered significantly 3 months after treatment. A retrospective analysis of 181 patients with nasopharyngeal carcinoma (NPC), including 60 cases of Uygur nationality and 121 cases of Han nationality, was made. The OS,DFS,LC,RC,DMFS in the whole group for 5 years was 80.2 and 67.9, respectively. There was no difference between Uygur and Han patients. The influencing factors of OS in Uygur patients were age; the influencing factors of DFS were age and N stage; the influencing factors of OS in Han nationality were age, N stage; the influencing factors of DFS were age. The mucosal reaction of Uygur patients after radiotherapy is lighter than that of Han patients. Conclusion: there are differences in heredity, T cell immunity and prognostic factors between Xinjiang Uygur and Han nationality patients with nasopharyngeal carcinoma.
【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R739.63

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