人白细胞抗原G基因多态性与非小细胞肺癌易感性的相关性研究

Research on the relationship between polymorphism of human leukocyte antigen-G and non-small cell lungcancer susceptibility

目的:探讨人白细胞抗原G(HLA-G)基因变异体和血清可溶性HLA-G(s HLA-G)水平与非小细胞肺癌(NSCLC)易感性的关系。方法:2012年1月至2015年1月间,180例NSCLC患者和180例健康受试者参与本项研究。通过免疫法检测血清s HLA-G水平,使用直接DNA测序技术检测HLA-G等位基因。结果:HLA-G 010101和HLA-G 010401杂合子基因型与NSCLC(χ~2=3.268,P=0.025和χ~2=2.563,P=0.036)发病和NSCLC晚期(χ~2=3.672,P=0.015和χ~2=3.257,P=0.028)风险的增加显著相关。HLA-G 0105N和HLA-G 0106杂合子基因型与NSCLC发病(χ~2=2.565,P=0.041和χ~2=3.569,P=0.017)和NSCLCⅣ期(χ~2=3.503,P=0.018和χ~2=2.586,P=0.036)风险的降低显著相关。NSCLC和晚期患者血清s HLA-G水平均高于健康人群。血清s HLA-G浓度高于32 U/ml的患者的生存期较短。结论:HLA-G基因变异体是NSCLC的独立风险因素,且NSCLC患者血清s HLA-G水平可能成为NSCLC诊断和预后的生物标志物。

Objective： To investigate the relationship between human leukocyte antigen-G（ HLA-G）allelic variants,serum soluble HLA-G（ s HLA-G） levels and non-small cell lung cancer（ NSCLC） susceptibility. Methods： 180 NSCLC and 180 healthy subjects were collected between January 2012 and January 2015.Serum s HLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. Results： The heterozygous genotypes of HLA-G 010101 and HLA-G 010401 were associated with increased risks of both NSCLC（ χ~2= 3. 268,P = 0. 025 and χ~2= 2. 563,P = 0. 036） and advanced disease stages（ χ~2= 3. 672,P = 0. 015 and χ~2= 3. 257,P = 0. 028）. The heterozygous genotypes of HLA-G0105 N and HLA-G 0106 were associated with decreased risks of NSCLC（ χ~2= 2. 565,P = 0. 041 and χ~2=3. 569,P = 0. 017） and clinical disease stage IV（ χ~2= 3. 503,P = 0. 018 and χ~2= 2. 586,P = 0. 036）,respectively. Serum s HLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. Patients with the s HLA-G above median level 32 U/ml had a significantly shorter survival time. Conclusion： This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum s HLA-G levels in NSCLC patients could be a biomarkers for the diagnostic and prognosis of NSCLC.