The analysis of senescence as a cancer suppressing mechanism in pancreatic carcinogenesis and its introduction to the diagnostic and therapeutic strategy

我们分析了衰老相关标记物，包括衰老相关β-半乳糖苷酶(SA-β-GAL)、衰老相关异染色质灶(SAHF)、p16INK4A和p15INK4b在正常胰腺、胰腺癌和导管内乳头状黏液肿瘤组织中的表达水平。结果发现，正常胰腺组织中阳性率最低，伴低度异型增生的IPMN阳性率最高。此外，从伴有低度不典型增生的IPMN向伴有浸润性癌的IPMN的转变有显著减少的趋势。这些结果表明，衰老是在IPMN的早期阶段诱导的，并随着时间的推移逐渐减弱。提示衰老在阻止IPMN的恶性进展中起一定作用。此外，我们还建立了可靠的方法来定量检测胰液和FNA细胞学标本中microRNA和mRNA的表达水平。这些方法是在术前和不能切除的病例中进行个体化治疗的有效策略。

We analyzed the expression levels of senescence associated markers, including senescence-associated β-galactosidase (SA-β-gal), senescence-associated heterochromatin foci (SAHF), p16INK4A, and p15INK4B, in normal pancreas, pancreatic cancer, and intraductal papillary mucinous neoplasm (IPMN) tissues. As the result, we found that the percentage of positive cases was lowest in normal pancreas and it reached a peak in IPMN with low-grade dysplasia. Furthermore, it showed significant decreasing trends in the transition from IPMN with low-grade dysplasia to IPMN with an associated invasive carcinoma. These results indicated that senescence is induced in the early stage of IPMN and gradually attenuated according to the progression. It is suggested that senescence plays a role in preventing malignant progression of IPMN. Additionally, we established the reliable methods to quantify the expression levels of microRNA and mRNA in pancreatic juice and FNA cytological samples. These methods are potent strategy to perform individualized therapy in preoperative and unresectable cases.