原发性肝细胞癌与HLA-DRB1基因多态性及DR抗原表达的关系

目的 探讨肝细胞癌(HCO与HLA-DRBl基因多态性及DR抗原表达的关系.方法 应用PCR-SSP方法与免疫组化技术对61例吉林地区汉族慢性乙型肝炎,44例乙型肝炎肝硬化病人,62例HCC病人及50名健康献血员作对照,进行了HLA-DRB1等位基因分型比较以及肝细胞癌癌组织、癌旁组织及正常肝组织的HLA-DR抗原表达进行检测.结果 慢性乙型肝炎组HLA-DRB1*1201-3等位基因表达频率为17.21%,明显高于正常对照组8.00%(P=0.0427,RR=2.391);慢性乙型肝炎组、乙型肝炎肝硬化组与肝癌组HLA-DRB1*0701等位基因频率分别为11.48%、12.50%、11.29%,明显高于正常对照组2.00%(P=0.0066,RR=6.35;P=0.0046,RR=7.00;P=0.0073,RR=6.236);HLA-DRB1*1501-5等位基因表达频率在肝癌组为18.55%,明显高于正常对照组9.00%(P=0.0423,RR=2.303);正常肝组织、肝癌旁组织肝细胞中HLA-DR抗原表达阴性,而34.2%的肝癌组织肝细胞膜和(或)胞浆中可见HLA-DR抗原表达,呈灶状分布,表达程度与肿瘤大小、癌周血管浸润及转移无关(P>0.05),与分化程度有关(P<0.05).结论 HLA-DRB1*1201-3、HLA-DRB1*0701等基因型与吉林地区汉族人群慢性乙型肝炎患病相关联,乙型肝炎肝硬化患病与HLA-DRB1*0701等位基因型相关联,肝癌患病与HLA-DRB1*1501-5、HLA-DRB1*0701等位基因型及DR表达量相关联.

Association of HLA-DRB1 gene polymorphism and expression of DR antigen with primary hepatocellular carcinoma

Objective To investigate the association of human leucocyte antigen-DRB1 alleles and expression of HLA-DR antigen with Hepatocellular carcinoma(HCC) in Han population of Jilin area. Methods HLA-DRB1 alleles in 61 patients with chronic hepatitis B, 44 patients with hepatic cirrhosis, 62 patients with HCC, and 50 healthy controls were analyzed by using polymerase chain re-action/sequence specific primer technique. Meanwhile the expression of HLA-DR antigen in HCC tis-sues, tissues adjacent to HCC and nomal liver tissues was detected with immunohistochemical method. Results The frequency of HLA-DRB1 * 1201-3 allele in chronic hepatitis B group was higher than that in healthy control group(17. 21% vs. 8. 00% ,P=0. 0427, RR=2. 391). The frequency of HLA-DRB1 * 0701 allele in chronic hepatitis B group, hepatic cirrhosis group and HCC group was markedly higher than that in healthy control group(11. 48% vs. 2. 00%, P=0. 0066, RR=6.35; 12.50% vs.2.00%, P=0.0046, RR=7.00; 11.29% vs. 2.00%, P=0.0073, RR=6.236). The frequency of HLA-DRB1 * 1501-5 allele in HCC group was higher than that in healthy control group(18. 55% vs.9.00%, P=0. 0423, RR= 2. 303). The expression of HLA-DR antigen was negative in hepatocytes of nomal liver tissues and tissues adjacent to HCC, while 34.2% of HCC tissues expressed DR antigen which distributed on the cytomembrane and/or in cytoplasm intensively. Expression of DR antigen in HCC was not associated with tumor size, tumor lymphocyte infiltration and tumor metastasis(P>0.05) ,but it was associated with histological grade. The rate of HLA-DR antigen expression in well-differenciated cases was higher than that in poorly-differenciated ones(P<0. 05). Conclusions Alleles of HLA-DRB1 * 1201-3 and HLA-DRB1 * 0701 were closed associated with chronic hepatitis B. HLA-DRB1 * 0701 was also closed associated with hepatic cirrhosis. Alleles of HLA-DRB1 * 1501-5, HLA-DRB1 * 0701 and expression quantity of HLA-DR antigen were associated with HCC in Han popula-tion of Jilin area.