Conclusions
Our study reveals that PDE4D up-regulated in PDAC was closely associated with poor prognosis of PDAC patients and multiple aggressive clinicopathological characteristics. PDE4D could be a useful prognostic biomarker and therapeutic target for PDAC.
Methods
Immunohistochemistry (IHC) was used to examine the expression of PDE4D in 104 clinicopathologically characterized PDAC cases. PDE4D expression in paired tumor tissues and adjacent noncancerous tissues were detected by western blotting and real time qRT-PCR. The correlation of PDE4D expression levels with clinicopathological features and prognosis in patients were analyzed by univariate and multivariate methods. Effect of PDE4D on pancreatic cancer cells was detected by cell migration and invasion assays.
Results
We found that PDE4D was significantly up-regulated in PDAC tumor tissues compared to those paired adjacent noncancerous tissues at both protein and mRNA levels. High level of PDE4D was significantly associated with clinical stage (P = 0.004), T classification (P = 0.003), lymph node metastasis (P = 0.022) and liver metastasis (P = 0.038). Patients with higher levels of PDE4D had shorter overall survival time contrast with those with lower PDE4D expression (P = 0.002). Multivariate analysis indicated that PDE4D may be an independent prognostic factor for PDAC. PDE4D depletion significantly suppressed β-catenin and Snail expression as well as the migration and invasion abilities of pancreatic cancer cells. Conclusions: Our study reveals that PDE4D up-regulated in PDAC was closely associated with poor prognosis of PDAC patients and multiple aggressive clinicopathological characteristics. PDE4D could be a useful prognostic biomarker and therapeutic target for PDAC.