High Phosphorylation Status of AKT/mTOR Signal in DESI2-Reduced Pancreatic Ductal Adenocarcinoma

Desumoylating isopeptidase 2 (DESI2) is a recently identified protein with unclear functions. In this study, a total of 132 tissue samples of pancreatic ductal adenocarcinoma and 73 samples of pancreatic normal tissues were explored to assess DESI2 expression and its implications to AKT/mTOR signal. Immunohistochemistry showed DESI2 expression is significantly decreased in cancer tissues versus normal tissues, presenting lowest level in poorly differentiated cancer. Unlike DESI2, the key factors in AKT/mTOR pathway including p-AKT, mTOR, p-mTOR and p-P70S6K present high expression in pancreatic cancer. It is notable that p-mTOR is significantly increased in DESI2-lower cancer compared with DESI2-higher cancer, although mTOR presents no difference in the two groups. The relative p-mTOR/mTOR ratio is also significantly elevated in DESI2-lower cancer. Moreover, the samples whose p-AKT and p-mTOR scores both exceed the median are obviously increased in DESI2-lower cancer compared with DESI2-higher cancer. As a downstream molecule of AKT/mTOR pathway, p-P70S6K was found to display higher level in DESI2-lower pancreatic cancer. High phosphorylation status of those proteins in DESI2-reduced pancreatic cancer indicates that there is high activity of AKT/mTOR signal in condition of DESI2 reduction, which could provide clues to reveal the implications of DESI2 in carcinogenesis.