大量研究表明，慢性胰腺炎与胰腺癌关系密切，但胰腺炎癌转化的具体分子机制尚不明确。我们前期发现，在急性胰腺炎、慢性胰腺炎及胰腺癌组织标本中Hedgehog-GLI1信号通路及DNA 甲基转移酶（DNMT1、DNMT3a）表达均明显升高，转录因子GLI1 可以调控DNMT1/3a的表达，而且DNMT1是GLI1转录调控的直接靶基因。由于DNMT 与DNA 的甲基化程度密切相关，因此我们推测在胰腺炎癌转化的过程中，Hedgehog-GLI1通过调节DNMT1/3a而影响相关基因甲基化水平从而导致胰腺炎癌转化的发生。本研究将从分子水平到整体层面以及动物模型、临床样本进行多维研究，探讨 Hh-GLI1-DNMTs 轴对基因甲基化修饰及胰腺炎癌转化的影响，以上研究将搭建起Hh信号通路与表观遗传修饰的桥梁，有助于阐明胰腺癌发生发展的分子机制，为胰腺癌的早期诊断及治疗提供新的思路。

A large number of studies have shown that chronic pancreatitis and pancreatic cancer are closely related, but the mechanism of pancreatitis malignant transformation is not clear. In our previous study it was found that the expression of Hedgehog/GLI1 (Hh-GLI1) and DNA methytransferase 1 and -3a (DNMT1/3a) were obviously up-regulated in acute pancreatitis, chronic pancreatitis, pancreatic cancer, DNMT1/3a could be regulated by transcription factor GLI1, and in addition DNMT1 was a direct target of GLI1. Because DNMT is the most important catalysis during DNA methylation, it broadly affects DNA methylation level, so we propose Hh-GLI1 could contribute to pancreatitis malignant transformation by regulating DNMT1/-3a and the methylation level of related genes. This multidimensional study, from the molecular level to the overall level as well as in animal models and clinical samples, will help to clarify the regulative function of Hh-GLI1-DNMTs axis on DNA methylation and pancreatitis malignant transformation. It would set a bridge between Hh-GLI1 pathway and epigenetic modification, and then elucidate the molicular mechanisms underlying pancreatitis malignant transformation and provide new ideas for the early diagnosis and treatment of pancreatic cancer.