DNA甲基转移酶1和组蛋白脱乙酰基酶1在胰腺组织中的表达及其临床意义

背景：近年针对DNA甲基化和组蛋白乙酰化修饰的表观遗传学研究是探索胰腺癌发生机制的新热点。目的：研究DNA甲基转移酶1（DNMT1）和组蛋白脱乙酰基酶1（HDAC1）在胰腺上皮内瘤变（PanIN）和胰腺癌组织中的表达．探讨其可能的临床意义。方法：以免疫组化SP法检测DNMT1、HDAC1在10例正常胰腺组织、39例证实含有PanIN的胰腺癌旁组织和54例胰腺导管腺癌（PDAC）组织中的表达。结果：DNMT1和HDAC1在胰腺组织中的阳性表达率均随组织异型程度的增加而逐渐增高，即正常胰腺导管（0％）〈PanIN—IA（7．2％±1．2％，10．7％±5．0％）〈PanIN-1B（24．5％±9．6％，40．1％±8．0％）〈PanIN-2（30．0％±11．9％，51．2％±13．4％）〈PanIN-3（46．7％±11．2％，73．1％±11.3％）〈PDAC（56．7％±27．5％，82．5％±19.4％），差异均有统计学意义（P〈0．05）。结论：DNMT1和HDAC1表达增强是胰腺癌发生的早期事件．两者共同促进了胰腺癌的进展，可能成为胰腺癌早期诊疗的新靶点。

Expressions of DNA Methyltransferase 1 and Histone Deacetylase 1 in Pancreatic Tissues and their Clinical Significances

Background： Recently, study on epigenetic modification of DNA methylation and histone acetylation in the pathogenesis of pancreatic cancer has been a new hot spot. Aims： To investigate the expressions of DNA methyltransferase 1 （DNMT1） and histone deacetylase 1 （HDAC1） in pancreatic intraepithelial neoplasia （PanIN） and pancreatic cancer tissues, and to approach their clinical significances. Methods： Expressions of DNMT1 and HDAC1 in 10 cases of normal pancreatic tissue, 39 cases of pancreatic paracancerous tissue containing PanIN and 54 cases of pancreatic ductal adeuocarcinoma （PDAC） tissue were determined by immunohistochemical SP method. Results： The expression rates of DNMT1 and HDAC1 in pancreatic tissues were gradually increased with the progress of the grade of dysplasia. The normal pancreatic duct （0%）〈 PanIN-1A （7.2%±1.2%, 10.7%±5.0%）〈 PanIN-1B （24.5%±9.6%, 40.1%±8.0%）〈 PanIN-2 （30.0%± 11.9%, 51.2%±13.4%）〈 PanIN-3 （46.7%±11.2%, 73.1%±11.3%）〈 PDAC （56.7%±27.5%, 82.5%±19.4%）, significant differences were found statistically （P〈0.05）. Conclusions： High expressions of DNMT1 and HDAC1 are early events during pancreatic carcinogenesis. DNMT1 and HDAC1 co-promote the progression of pancreatic cancer, which may be the new target markers for its early diagnosis and treatment.