胆汁中K-ras基因突变对胰腺癌肝转移诊断价值的实验研究

Experiment Study on the Diagnostic Value of Bile K-ras Gene Mutation Responsible to the Hepatic Metastasis of Pancreatic Cancer

目的探讨胆汁中K-ras基因突变检测在胰腺癌肝转移早期诊断中的价值。方法通过建立胰腺癌及胰腺癌肝转移的大鼠动物模型,收集模型大鼠的胆汁,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)检测胆汁中K-ras基因12密码子点突变情况并与病理切片法相比较。结果16例胰腺癌动物模型胆汁标本中无K-ras基因突变(0/16),19例胰腺癌肝转移动物模型胆汁标本中K-ras基因突变率为84.20%(16/19)。胰腺癌肝转移胆汁K-ras基因突变检测的敏感性为84.20%,特异性为85.7%,阳性预测值为84.20%,阴性预测值为85.70%。结论胰腺癌肝转移胆汁中K-ras基因可以发生突变,其突变率高,特异性强,可能为胰腺癌肝转移早期诊断的初步筛选提供新的方法。

Objective To investigate the early diagnosis value of bile K-ras mutation responsible for hepatic metastasis of pancreatic cancer. Methods While building the animal models with pancreatic cancer and hepatic metastasis of pancreatic cancer of rats, we collected bile from the model animals, and used the polymerase chain reaction and restriction fragment-length polymorphism （PCR-RFLP） to evaluate the point mutation at exon codon 12 of K-ras gene in bile. Then, the above result was compared with pathological slice. Results The positive rates of K-ras point mutation in bile were 84. 2% （16/19） for the model with hepatic metastasis of pancreatic cancer, and 0. 0% （0/16） for the model with pancreatic cancer without hepatic metastasis. For the model with hepatic metastasis of pancreatic cancer, the sensitivity, specificity, positive prediction or negative prediction value of surveying K-ras mutation in bile was 84. 2%, 85. 7%, 84. 2% or 85. 7% respectively. Conclusion Both the mutability and the specificity of K-ras gene mutation at codon 12 in bile are high. Our above work can supply a new elemental filter method for the early diagnosis of hepatic metastasis of pancreatic cancer.