中国宁夏人群HOTAIR单核苷酸多态性与胃癌易感性的相关性研究

目的探索中国宁夏人群中HOTAIR单核苷酸多态性与胃癌(gastric cancer, GC)易感性的相关性研究.方法挑选3个H O TA I R基因位点r s12826786(C>T),rs920778(C>T), RS4759314(A>G),对其多态性进行了基因分型;选取152名GC患者和307名健康对照者,按照年龄,体重,性别等因素相匹配,通过PCR与高通量TaqMan分析其单核苷酸多态性对于GC遗传易感性的影响.结果HOTAIRRs920778位点基因型TT在病例组和对照组中的频率分别为26.3%和24.7%,基因型C/T在两组中的频率分别为21.1%和31.3%,基因型CC在两组中的频率分别为52.6%和44.0%,该位点的TT基因型与GC的遗传易感性具有显著联系,结果具有统计学意义(P <0.05).Rs12826786和Rs4759314两个基因位点与GC发病危险关系的结果并无统计学意义(P>0.05).进一步的分层分析中发现Rs920778位点的单核苷酸多态性与男性,吸烟人群及肿瘤大小≥5 cm的GC患者的GC遗传易感性高度相关,而与患者的年龄因素,女性患者,非吸烟患者,患者的远处转移情况及GC家族史并无显著联系.结论中国宁夏人群中HOTAIR Rs920778位点单核苷酸多态性与GC的遗传易感性具有一定程度的联系.

Association between circulating CD39+CD8+T cells prechemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma

Background:The mortality rate among patients with nasopharyngeal carcinoma(NPC)has improved significantly with the advent of chemoradiotherapy strategies.However,distant metastasis remains problematic.Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+T cells,particularly in CD39+CD103+T cells.Circulating cancer-specific T cells are important for protecting against metastasis.This study aimed to evaluate the predictive value of circulating CD39+CD8+T cells for metastasis in patients with NPC.Methods:We performed a cross-sectional,longitudinal study of 55 patients with newly diagnosed NPC of stage III–IVa.All patients were initially treated with standard combined chemoradiotherapy.Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment.T cell expression of CD39 and CD103,together with the markers of T cell exhaustion programmed death-1(PD-1)/T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA,was examined by flow cytometry.The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups.Kaplan-Meier analysis was used for analysis of progression-free survival(PFS).Results:The expression of circulating CD39+CD8+and CD39+CD103+CD8+T cells was significantly higher in patients without distant metastasis(CD39+CD8+:6.52%[1.24%,12.58%]vs.2.41%[0.58%,5.31%],Z=2.073,P=0.038 and CD39+CD103+CD8+:0.72%[0.26%,2.05%]vs.0.26%[0.12%,0.64%],Z=2.313,P=0.021).Most CD39+T cells did not express PD-1 or Tim-3.Patients with high expression of CD39+CD103+CD8+T cells had better PFS than patients with low expression(log rank value=4.854,P=0.028).CD39+CD8+T cells were significantly elevated at 1-month post-treatment(10.02%[0.98%,17.42%]vs.5.91%[0.61%,10.23%],Z=2.943,P=0.003).The percentage of advanced differentiated CD8+T cells also increased at 1-month post-treatment compared with pre-treatment(33.10%[21.60%,43.05%]vs.21.00%[11.65%,43.00%],Z=2.155,P=0.031).There was a significant correlation between elevated CD39+CD8+T cells and increased effector memory T cells(intermediate stage:r=0.469,P=0.031;advanced stage:r=0.508,P=0.019).Conclusions:CD39+CD8+circulating T cells have preserved effector function,contributing to an improved prognosis and a reduced risk of metastasis among NPC patients.These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 T Cell Response in Blood

Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the T cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of T cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.