Amplification of chromosome 21q22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis

瞄准：在 cholangiocarcinoma (CCA ) 包括翘摇因素家庭基因(TFF ) 在染色体区域 21q22-qter 上决定突变而产生之遗传的不平衡病人和分析在突变而产生之遗传的不平衡和 clinicopathological 参数之间的关联。方法：量的 PCR 扩大用一条标准曲线和格林·西布尔在四个微卫星标记和翘摇因素家庭基因(TFF1， TFF2，和 TFF3 ) 上被执行我染料方法。相对拷贝数字被测试地点的 DNA 拷贝数字决定引用地点。当由有正常参考的比较的删除或扩大变化，相对拷贝数字被解释。在突变而产生之遗传的不平衡和 CCA 病人的 clinicopathological 参数之间的协会被 chi (2 ) 评估测试。Kaplan-Meier 方法被用来分析幸存。结果：在 D21S1890， D21S1893，和 TFF3 的扩大的频率分别地是 32.5% ， 30.0% ，和 28.7% 。在盖住 D21S1893， D21S1890，和 TFF 的区域有扩大的病人显示出差的预后，而有删除的病人显示出有利预后(平均数：51.7 wk 对 124.82 wk， P = 0.012 ) 。穆尔蒂瓦里伊特·考克斯回归分析表明 D21S1893， D21S1890 和 TFF，血管侵略，和阶段的那扩大与差的预后被联系。结论：D21S1893-D21S1890 区域可以特别怀有候选人基因 TFF 和丝氨酸朊酶家庭，它可能涉及肿瘤侵略和转移贡献穷人幸存。在这个区域的扩大可以在 CCA 病人的治疗被用作一个预示的标记。

AIM： To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes （TFF） in cholangiocarcinoma （CCA） patients and analyze the correlation between allelic imbalances and clinicopathological parameters. METHODS： Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes （TFF1, TFF2, and TFF3） using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ^2-tests. Kaplan-Meier method was used to analyze survival. RESULTS： The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis （mean： 51.7 wk vs 124.82 wk, P = 0.012）. Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis. CONCLUSION： D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.