胰腺癌DPC4/Smad4基因突变及表达

DPC4 gene mutation and abnormal expression in pancreatic carcinoma

目的:探讨胰腺癌DPC4/Smad4基因突变和表达的意义及临床应用价值,并分析了DPC4/Smad4基因表达与胰腺癌病理特征的关系。 方法:采用聚合酶链反应-单链构像多态性分析(PCR-SSCP)-银染技术和直接测序法检测了胰腺癌组织中DPC4/Smad4基因第8及第11外显子突变,并采用原位杂交方法检测DPC4/Smad4 mRNA的表达。 结果:23例胰腺癌中2例DPC4第8外显子DNA片段出现异常泳动带,1例DPC4第11外显子出现异常泳动带,突变率为13.04％。对其中阳性标本进行测序,1例表现为点突变。DPC4/Smad4 mRNA在胰腺癌组织表达的阳性率52.2％(12/23),较癌周胰腺组织90％(9/10)表达阳性率降低(P<0.05),随着胰腺癌分化程度不同,表达的阳性率不同,分化程度越差,表达率越低;分化程度越好,表达率越高,表明DPC4/Smad4基因表达与肿瘤的分化程度呈正相关,而与胰腺癌病理分期、淋巴结转移无显著相关(P>0.05),胰腺癌DPC4/Smad4 mRNA在Ⅰ,Ⅱ期表达率63.6％(7/11)与Ⅲ,Ⅳ期表达率41.7％(5/12)相近(P>0.05),伴有淋巴结转移胰腺癌DPC4/Smad4 mRNA表达率41.7％(5/12)与不伴有淋巴结转移者表达率63.6％(7/11)也相似(P>0.05)。 结论:胰腺组织与胰腺癌组织可存在DPC4/Smad4 mRNA表达的差异,DPC4/Smad4 mRNA的表达与胰腺癌分化程度相关。DPC4基因的失活在胰?

AIM: To observe the expression and mutation of DPC4/ Smad4 mRNA in pancreatic carcinoma and to analyse the relations between expression and mutation of DPC4/ Smad4 mRNA and clinicopathological manifestation in pancreatic carcinoma (PC).METHODS: In this study, the expression and mutation of DPC4/ Smad4 gene were detected in 23 cases of PC by using the polymerase chain reaction, single-strand conformation polymorphism analysis ( PCR-SSCP ) and in situ hybridization.RESULTS: Mutations of DPC4 at exon 8,11 were detected in 3 cases (13.04 %), in which a mobility shift of complementary DNA fragment to exon 11 of DPC4 was found in 1 case, and to exon 8 in 2 cases. Mutation of OPC4/ Smad4 was confirmed in one case using DNA sequencing. The positive rates of DPC4/ Smad4 expression in PC and precancerous tissue were 52.2 % and 90 %(P< 0.05), respectively. The expression of DPC4/ Smad4 gene was related to the degrees of cell differentiation of PC, and the rate of DPC4/ Smad4 mRNA expression abnormality in pathologic stage Ⅰ - Ⅱ was 63.6%(7/11) and pathologic stage Ⅲ-Ⅳ, 41.7 % (5/ 12), with no statistic significance(P< 0.05). Expression rate of DPC4/ Smad4 mRNA in lymph node metastasis of pancreatic carcinoma was 41.7 % (5/12) and that without lymph node metastasis was 63. 6 % (7/ 11), also with no statistically significant difference(P< 0.05).CONCLUSIONS: Abnormal expression of DPC4/Smad4 mRNA often occurs in pancreatic cancer. DPC4/Smad4 is frequently inactivated in PC, in which exon 8 and exon 11 are the hot point. Inactivation of DPC4/ Smad4 may play an important role during the carcinogenesis of pancreatic carcinoma.