微小RNA-34a和微小RNA-204可有效用于早期诊断胰腺导管上皮内瘤变的实验研究

Early diagnosis of pancreatic ductal intraepithelial neoplasia by microRNA-34a and microRNA-204

目的探讨微小RNA(microRNA,miRNA)-34a和miRNA-204的异常表达是否能用于区别慢性胰腺炎(CP)与胰腺导管上皮内瘤变(PanINs)。方法用部分结扎大鼠胆胰管和置入7,12-二甲基苯并蒽(DMBA)的方法建立SD大鼠(华中科技大学实验动物中心提供)CP-胰腺癌模型,获得16个CP标本和26个PanINs标本。然后用实时定量聚合酶链反应(RT-PCR)检测4种与胰腺癌相关的miRNAs(miR-34a、miR-204、miR-107和miR-21)在这些标本中的表达。两组之间的差异用方差分析、Kruskal-Wallis检验或Student’s t检验进行统计学分析。结果miR-34a在PanIN-1(1.81±0.12比1.00±0.08,t=2.032,P<0.05)、PanIN-2(1.72±0.11比1.00±0.08,t=1.332,P<0.05)和PanIN-3(2.62±0.14比1.00±0.08,t=4.135,P<0.05)标本中的表达显著高于CP组,差异有统计学意义。miR-204在PanIN-2(0.59±0.08比1.00±0.12,t=5.037,P<0.05)和PanIN-3(0.51±0.07比1.00±0.12,t=5.385,P<0.05)标本中的表达显著低于CP组,差异有统计学意义。miR-21只在PanIN-3(2.23±0.21比1.00±0.12,t=4.485,P<0.05)标本中表达显著高于CP组,差异有统计学意义。结论miR-34a和miR-204在CP发展到胰腺癌的过程中表达异常,可用于区别CP与PanINs。

Objective To investigate whether the expression of microRNA(miR)-34a and miR-204 is a potential biomarker to distinguish chronic pancreatitis(CP)from pancreatic intraepithelial neoplasias(PanINs).Methods In this study,four miRNAs(miR-34a,miR-204,miR-107 and miR-21)related to pancreatic ductal adenocarcinoma(PDAC)were selected.Pancreatic samples of 16 CP and 26 PanIN lesions were obtained from a CP-PDAC rat model which was induced by partial ligation of biliary-pancreatic ducts and implantation of 7,12-dimethylbenzanthracene(DMBA)in rats for 16 weeks.The expression of miRNA was detected in the samples using the quantitative real-time polymerase chain reaction(RT-qPCR)technique.The differences between the two groups were statistically analyzed by variance analysis,Kruskal-Wallis test or Student′s t test.P<0.05 represents statistical significance and significant difference.Results Relative to CP,the significant overexpression of miR-34a was observed in PanIN-1(1.81±0.12 to 1.00±0.08,t=2.032,P<0.05),PanIN-2(1.72±0.11 to 1.00±0.08,t=1.332,P<0.05)and PanIN-3(2.62±0.14 vs.1.00±0.08,t=4.135,P<0.05),while significantly low expression of miR-204 was observed in PanIN-2(0.59±0.08 to 1.00±0.12,t=5.037,P<0.05)and PanIN-3(0.51±0.07 to 1.00±0.12,t=5.385,P<0.05).In contrast,significant overexpression of miR-21 was observed in PanIN-3(2.23±0.21 to 1.00±0.12,t=4.485,P<0.05)only by RT-qPCR.Conclusion Our study demonstrates that the abnormal expression of miR-34a and miR-204 during the development of chronic pancreatitis to pancreatic cancer can be used to distinguish CP from PanINs.