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目的探讨合并慢性胰腺炎的胰腺癌癌旁增生性胰管上皮细胞线粒体DNA调控序列(D-loop)突变的意义。方法利用PCR技术,扩增胰腺导管增生性细胞、癌细胞及其各自正常的胃黏膜上皮细胞的线粒体DNA D-loop。核苷酸序列同源性对比分析,观察病变细胞的D-loop突变频率。结果癌细胞和增生性病变细胞至少存在一个以上的突变点,总突变点为31。突变类型:线粒体DNA 11/12为同质性突变,1/12为异质性突变。D-loop突变频率随病变进展程度呈进行性增加的趋势,异常D-loop由PanIN1的33.3%增加到PanIN3的75.0%(P<0.01)。结论胰腺导管上皮细胞病变存在着异常D-loop,D-loop异常程度与病变发展程度呈平行性发展。异常D-loop可作为检测胰腺导管上皮性细胞病变的标志物。
Objective To investigate the significance of mitochondrial DNA regulatory sequence (D-loop) mutation in para-cancerous hyperplastic pancreatic epithelial cells in pancreatic cancer with chronic pancreatitis. Methods PCR technique was used to amplify mitochondrial DNA D-loops of pancreatic ductal proliferative cells, cancer cells and their respective normal gastric epithelial cells. Nucleotide sequence homology analysis was performed to observe the D-loop mutation frequency of diseased cells. Results There were at least one mutation point in cancer cells and hyperplastic lesions, with a total mutation point of 31. Types of mutations: Mitochondrial DNA 11/12 is a homogenous mutation and 1/12 is a heterogeneity mutation. The frequency of D-loop mutations showed a progressive increase with the extent of disease progression. Abnormal D-loop increased from 33.3% of PanIN1 to 75.0% of PanIN3 (P<0.01). Conclusion There is abnormal D-loop in the pathological changes of pancreatic ductal epithelial cells. The abnormal degree of D-loop parallels the progression of the lesions. Abnormal D-loop can be used as a marker to detect pancreatic ductal epithelial cell lesions.