pre-miR-146a基因rs2910164位点单核苷酸多态性与胆管癌的关系

Association of single nucleotide polymorphism of rs2910164 in pre-miR-146a sequence with cholangiocarcinoma

目的:探讨pre-miR-146a基因表达及其rs2910164位点多态性与胆管癌的关系。方法:分别用基因直接测序与定量PCR方法检测70例胆管癌患者的胆管癌组织(胆管癌组)及39例胆管非肿瘤性疾病患者的胆管组织(对照组)中pre-miR-146a基因rs2910164位点单核苷酸多态性与pre-miR-146a表达,分析不同基因型与pre-miR-146a表达量、胆管癌临床病理及其预后的关系。结果:胆管癌组的pre-miR-146a基因型分布与对照组有明显差异,前者表现为GG和GC基因型比例明显高于CC基因型,且G等位基因频率明显高于C等位基因(均P<0.05);对照组GG和GC基因型人群的pre-miR-146a表达量较CC基因型低,但差异无统计学意义(P>0.05),胆管癌组织pre-miR-146a表达量明显低于对照组胆管组织(P<0.05);Logistic多元回归分析显示GG和GC基因型可能是胆管癌的危险因素(P=0.052),分层分析显示GG和GC基因型与胆管癌患者的临床分期和淋巴结转移有关(均P<0.05);生存分析显示GG和GC基因型胆管癌患者的生存率低于CC基因型胆管癌患者,但差异无统计学意义(P=0.178)。结论:pre-miR-146a基因rs2910164位点G等位基因频率升高可能是导致pre-miR-146a基因表达降低以及胆管癌发生发展的危险因素。

Objective： To investigate the relations ofpre-miR-146a gene expression and its rs2910164 allelic polymorphism with cholangiocarcinoma. Methods： In 70 specimens of cholangiocarcinoma tissues from bile duct cancer patients （cholangiocarcinoma group） and 39 specimens of bile duct tissues from cases with non-neoplastic bile duct diseases （control group）, the single nucleotide polymorphism of rs2910164 in pre-miR-146a sequence and pre-miR-146a expression was determined by direct DNA sequencing and the quantitative PCR method, respectively. The relationsof different pre-miR-146a genotypes with its expression, and clinicopathological profiles and prognosis of cholangiocarcinoma were analyzed. Results： q-he genotype distribution in cholangiocarcinoma group was significantly different from that in control group, which in the former showed that the ratio of GG and GC genotypes was significantly higher than that of CC genotype, and the frequency of G allele was significantly higher than that of C allele （both P〈0.05）. In control group, the pre-miR-146a expression level in cases with GG and GC genotypes was lower than that in cases with CC genotype, but the difference did not reach a statistical significance （P〉0.05）, while the pre-miR- 146a expression level in cholangiocarcinoma tissues was significantly lower than that in the bile duct tissues from control group （P〈0.05）. Multiple logistic regression analysis showed that GG and GC genotypes were possibly the risk factors for bile duct cancer （P=0.052）, and the further factor-stratified analysis showed that GG and GC genotypes were associated with the clinical stage and lymph node metastasis of the patients （both P〈0.05）. Survival analysis for the cholangiocarcinoma patients demonstrated that the survival rate in cases with GG and GC genotypes was lower than that in cases with CC genotype, but the difference had no statistical significance （P=0.178）.Conclusion： The increased frequency of G allele at rs2910164 in pre-miR-146a sequence may be responsible for pre-miR- 146a gene under-expression and the risk factor for the occurrence and development of bile duct cancer.