AR基因CAG重复序列拷贝数与男性HBV相关性HCC临床特征关系研究

Relationship Between the Copy Number of AR Gene CAG Repeat Sequenceand the Clinical Characteristics of Male HBV-Associated HCC

为探讨男性HBV相关性肝细胞肝癌组织中雄激素受体(AR)第一外显子CAG重复序列数的临床病理学意义,收集83例男性HBV相关性肝细胞肝癌组织及癌旁肝组织,并以45例男性乙型肝炎患者肝脏穿刺组织作为对照,用荧光标记的引物聚合酶链反应(PCR)扩增AR基因CAG重复序列,并分析计算其重复序列数;用实时荧光定量PCR检测新鲜肝癌组织及癌旁肝组织中AR基因的mRNA相对表达水平.结果表明:男性HBV相关性肝细胞肝癌组织中AR基因CAG重复序列平均数明显低于男性乙型肝炎患者肝脏穿刺组织中该序列平均数(P<0.01);与癌旁肝组织相比,CAG重复序列数在8例男性HBV相关性肝细胞肝癌组织中出现变异(5例减少,3例增多);肝癌组织中AR基因的mRNA相对表达水平为0.21±0.02,癌旁肝组织中AR基因的mRNA相对表达水平为0.22±0.08,两者无明显差异(P>0.05);癌旁肝组织中CAG重复序列数与AR基因的mRNA相对表达水平呈负相关性(r=-0.67,P<0.01),肝癌组织中AR基因的mRNA相对表达水平与CAG重复序列数无相关性(r=0.12,P>0.05);肝癌组织中CAG重复序列数与病理分级、癌旁肝硬化情况、肿瘤复发情况、淋巴结转移、感染乙肝病毒的基因型等临床病理参数无明显相关性.可见,男性HBV相关性肝细胞肝癌组织中AR基因CAG重复序列数明显低于男性乙型肝炎患者,这可能是HBV相关性肝细胞肝癌发生的危险因素之一.

To investigate the clinicopathological significance of CAG repetitive sequence number of the first exon of androgen receptor(AR)in the HBV-associated hepatocellular carcinoma tissues of male patients,we collected cancerous and paracancerous tissues of 83 male HBV-associated hepatocellular carcinoma,and used the liver puncture tissues of 45 hepatitis B male patients as the control.CAG repetitive sequences of AR gene were amplified by PCR with fluorescent primers,and the number of repetitive sequences were analyzed and calculated.The relative expression level of AR mRNA in fresh cancer tissues and paracancerous tissues was detected by real-time fluorescence quantitative PCR.The results showed that the average number of CAG repetitive sequences of AR gene in the HBV-associated HCC tissues of male patients was significantly lower than that in male patients with hepatitis B(P<0.01);Compared with the adjacent tissues,CAG repeat number showed variation in 8 male patients with HBV-associated HCC(5 cases decreased and 3 cases increased);The relative expression level of AR mRNA in HCC tissue was 0.21±0.02,and that in paracancerous tissues was 0.02±0.08,there was no significant difference between the two groups(P>0.05);There was a negative correlation between the CAG repeat sequence and the relative expression level of AR mRNA in paracancerous tissues(r=-0.67,P<0.01),but no correlation between the relative expression level of AR mRNA and the CAG repeat number in HCC tissues(r=0.12,P>0.05);There was no significant correlation between the CAG repeat sequence number and clinicopathological parameters such as pathological grade,cirrhosis,recurrence,lymph node metastasis and HBV genotype.It can be seen that the CAG repeat number of AR gene in the male HBV-associated HCC tissue is significantly lower than that in male hepatitis B patients,which may be one of the risk factors for HBV-associated HCC.