HLA-A/B基因多态性与女性高危型HPV16/18感染和宫颈癌易感性的关联性分析OA
Association analysis of HLA-A/B gene polymorphism with high-risk HPV16/18 infection and susceptibility to cervical cancer in women
目的:探讨宫颈癌患者HLA-A/B基因多态性与高危型HPV16/18感染及宫颈癌易感性之间的关联.方法:选取2020年1月至2023年6月在广西医科大学第一附属医院确诊的宫颈癌患者作为观察组(n=205),选取同期参加宫颈癌筛查项目的健康女性作为对照组(n=97).PCR和测序法检测受试者HLA-A/B基因进行分型;PCR-荧光标记法检测受试者HPV基因分型;流式细胞术检测受试者宫颈脱落细胞中CD8+T细胞水平及其表面活性抑制分子PD-1、TIM-3阳性率;Spearman相关性分析HLA-A/B基因多态性与宫颈癌患者高危型HPV感染、宫颈癌易感性及CD8+T细胞功能间的相关性.结果:所有受试者中检测到11种HLA-A等位基因和22种HLA-B等位基因.观察组患者HLA-A*02、A*03、A*11、HLA-B*27和B*44等HLA-A/B等位基因出现频率明显高于对照组(均P<0.05).高危型HPV感染的宫颈癌患者HLA-A*02、A*11、HLA-B*07和B*44等HLA-A/B等位基因频率高于非高危型HPV感染的宫颈癌患者(均P<0.05).Spearman相关性分析表明,HLA-A*02和HLA-A*11与宫颈癌呈正相关(r=0.205、0.138,P=0.013、0.027),HLA-A*02和HLA-B*44分别与高危型和非高危型HPV感染呈正相关(r=0.123、0.253,P=0.008、0.020)、HLA-A*02、HLA-A*11和HLA-B*44分别与颈脱落细胞中CD8+T细胞水平(r=0.115、0.169、0.153,P=0.011、0.025、0.020)、PD-1阳性率(r=0.101、0.136、0.163,P=0.040、0.033、0.031)及TIM-3阳性率(r=0.124、0.201、0.211,P=0.005、0.008、0.009)均呈正相关.结论:携带HLA-A*02和A*11的个体与高危型HPV16/18感染呈显著正相关,而HLA-A*02和HLA-B*44为女性宫颈癌患者的易感基因,可能与CD8+T细胞免疫功能耗竭有关.
Objective:To investigate correlation between HLA-A/B gene polymorphisms in cervical cancer patients and susceptibility to high-risk HPV16/18 infection and cervical cancer.Methods:Observation group(n=205)consisted of cervical cancer patients diagnosed at the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023,while control group(n=97)comprised healthy women participating in hospital's cervical cancer screening program during same period.PCR and sequenc-ing methods were employed to detect HLA-A/B gene typing in subjects;PCR-fluorescence labeling was used to detect HPV gene typing in subjects;level of CD8+T cells and positive rate of PD-1 and TIM-3,which inhibit surface activity,were detected by flow cy-tometry;Spearman correlation analysis was conducted to assess relationship between HLA-A/B gene polymorphisms and susceptibility to high-risk HPV infection,cervical cancer and CD8+T cell function in patients.Results:Among all subjects,11 HLA-A alleles and 22 HLA-B alleles were detected.Frequencies of HLA-A*02,A*03,A*11,HLA-B*27 and B*44 alleles were significantly higher in observation group compared to control group(all P<0.05).In cervical cancer patients with high-risk HPV infection,frequencies of HLA-A*02,A*11,HLA-B*07 and B*44 alleles were higher than patients with non-high-risk HPV infection(all P<0.05).Spearman correlation analysis indicated that HLA-A*02 and HLA-A*11 were positively correlated with cervical cancer(r=0.205,0.138;P=0.013,0.027),while HLA-A*02 and HLA-B*44 were positively correlated with high-risk and non-high-risk HPV infections,respec-tively(r=0.123,0.253;P=0.008,0.020).HLA-A*02,HLA-A*11 and HLA-B*44 were associated with level of CD8+T cells(r=0.115,0.169,0.153,P=0.011,0.025,0.020),positive rate of PD-1(r=0.101,0.136,0.163,P=0.040,0.033,0.031)and positive rate of TIM-3(r=0.124,0.201,0.211,P=0.005,0.008,0.009)were positively correlated.Conclusion:Carriers of HLA-A02 and A11 are significantly positively associated with high-risk HPV16/18 infection.HLA-A*02 and HLA-B*44 are susceptibility genes for cervical cancer in women,these may be related to depletion of CD8+T cell immune function.
卢庭婷;黄海鹏;陈基强;张柯媛
广西卫生职业技术学院医学技术学院,南宁 530021桂林医学院继续教育学院,桂林 541001广西卫生职业技术学院医学技术学院,南宁 530021广西卫生职业技术学院医学技术学院,南宁 530021
医药卫生
宫颈癌HLA-A/B易感性高危型HPV基因多态性
Cervical cancerHLA-A/BSusceptibilityHigh-risk HPVGenetic polymorphism
《中国免疫学杂志》 2026 (3)
574-580,7
2023年度广西高校中青年教师科研基础能力提升项目(2023KY1413).
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