J Cancer 2019; 10(25):6252-6260. doi:10.7150/jca.35443

Research Paper

High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma

Fude Liu1*, Jieyi Ma2*, Kebing Wang2, Zhi Li3, Qingping Jiang4, Hui Chen4, Wen Li2✉, Jintang Xia1✉

1. Department of General Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China
2. Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
3. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
4. Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510150, China
*These authors contributed equally to this work

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Citation:
Liu F, Ma J, Wang K, Li Z, Jiang Q, Chen H, Li W, Xia J. High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma. J Cancer 2019; 10(25):6252-6260. doi:10.7150/jca.35443. Available from http://www.jcancer.org/v10p6252.htm

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Abstract

Background: Phosphodiesterase 4D (PDE4D) has recently been reported as an oncogene in various types of human cancers. However, the expression and significance of PDE4D in pancreatic ductal adenocarcinoma (PDAC) have not been elucidated.

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.

Keywords: phosphodiesterase 4D, pancreatic ductal adenocarcinoma, prognosis, β-catenin