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

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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.