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

我们分析了正常胰腺、胰腺癌和导管内乳头状粘液性肿瘤（IPMN）组织中衰老相关标志物的表达水平，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）、p16 INK 4A和p15 INK 4 B。结果发现，在正常胰腺中阳性率最低，在IPMN伴低度异型增生中阳性率最高。此外，它显示出显着的下降趋势，从IPMN与低度异型增生的IPMN与相关的浸润性癌的过渡。这些结果表明，衰老在IPMN的早期阶段被诱导，并随着进展而逐渐减弱。这表明，衰老在防止IPMN的恶性进展中起作用。此外，我们还建立了可靠的方法来定量测定胰液和FNA细胞学样品中microRNA和mRNA的表达水平。这些方法为术前不能手术切除的病例实施个体化治疗提供了有力的策略。

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.