胰腺癌β2肾上腺素能受体基因多态性的研究  

The study of single nucleotide polymorphisms of β2-adrenergic receptor in pancreatic carcinoma

作　　者：李玉军[1] 于文娟[1] 于层[1] 孙显路[1] 

机构地区：[1]青岛大学医学院附属医院病理科,266003

出　　处：《中华肝胆外科杂志》2013年第2期128-132,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：青岛市科技局项目[11-2-3-1-（15）-nsh]

摘　　要：目的探讨β2肾上腺素能受体（B2-AR）基因16、27位密码子单核苷酸多态性（SNPs）与胰腺癌临床病理特征、β2-AR蛋白表达情况的相关性。方法应用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法结合DNA测序法检测64例胰腺癌组织和20例癌旁胰腺组织中132-AR16、27位点的多态性。免疫组织化学技术检测肿瘤组织中β2-AR蛋白的表达情况。结果16、27位点的基因型多态性分布均符合Hardy-Weinberg平衡定律。16、27位点的基因型和等位基因分布频率在胰腺癌组和癌旁胰腺组间差异均无统计学意义（P〉0．05）。16位点基因型分布频率与患者的性别、年龄、肿瘤分化程度、肿瘤大小无相关性（P〉0．05），与淋巴结转移、TNM分期、1年生存率及β2-AR蛋白的表达水平相关（P=0．03、0．05、0．04）。G等位基因与淋巴结转移、高TNM分期、低1年生存率及β2-AR蛋白的高表达相关（P=0．01、0．03、0．02、0．02）。27位点基因型分布频率与患者的性别、年龄、肿瘤分化程度、肿瘤大小、淋巴结转移、TNM分期、1年生存期及β2-AR蛋白的表达水平均无相关性（P〉0．05）。结论β2-AR基因16位点SNPs与胰腺癌的生物学行为相关。G等位基因提示有淋巴结转移可能、TNM分期高、1年生存率低及p：一AR蛋白高表达。它可能通过增加β2-AR蛋白的表达促进胰腺癌进展与转移。检测β2-AR基因16位点SNPs有助于评估患者胰腺癌的生物学行为和预后，有望成为胰腺癌基因治疗的新靶点。Objective To investigate the single nucleotide polymorphisms （SNPs） at codons 16 and 27 of β2-AR gene in pancreatic carcinoma and non-neoplastic pancreatic tissues, and the correla tions between these SNPs and the expression of β2-AR protein in pancreatic carcinoma. Methods A total of 64 cases of pancreatic carcinoma （PC） and 20 non-neoplastic pancreatic tissues （NPC） were genotyped at codons 16 and 27 by PCR-restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing. The correlations between the distribution of genotypes and clinicopathological characteristics of pancreatic carcinoma were analyzed. The expression of β2-AR protein was detected by immunohistochemistry in pancreatic carcinoma. Results The distributions of genotype frequency at codons 16 and 27 in PC and NPC were in accordance with the Hardy-Weinbery equeilibrium. The frequencies of their genotypes （AA, AG and GG） and frequencies of alleles A and G at codon 16 between PC and NPC showed no difference. The genotype frequencies were associated with TNM grade, lymph node metastasis, one-year survival rate （P=0.03, 0.05, 0.04）, but they were not associated with patients＇ gender, age, histological differentiation and size of tumor. The allele G at codon 16 was frequently appeared in tumors with high TNM grade, lymph node metastasis, low one-year survival rate （P=0.01, 0.03, 0.02）, and high expressions of β2-AR protein （P=0.02）. The frequencies of two genotypes （CC and CG） and frequencies of alleles C and G at codon 27 showed no difference between PC and NPC. The genotype frequencies and allele frequencies of codon 27 were not associated with patients＇ clinicopathological features, and expressions of 132-AR protein. Conclusions SNPs of β2-AR gene were associated with biological behaviors of pancreatic carcinoma. Allele G at codon 16 was associated with high risks of lymph node metastasis, high TNM grade, low one-year survival rate, and high expressions of β2-AR protein. Allele G at codon 16 might fa

关 键 词：胰腺肿瘤 受体 肾上腺素能Β2 多态性 单核苷酸 

分 类 号：R735[医药卫生—肿瘤]