Abstract 5527: Overexpression of protein phosphatase 4 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma

Background: PP4 has been reported to be overexpressed in breast and lung cancers. While previous studies have identified the role of PP4 in activating NFκB and JNK signaling pathway, the expression and functions of PP4 in pancreatic cancer has not been studied in detail. Methods: We examined the expression of PP4 protein in 133 patient samples of stage II pancreatic ductal adenocarcinoma (PDA) samples by immunohistochemistry (IHC). To confirm our IHC results, we measured the expression levels of PP4 mRNA in 15 PDA samples and 15 benign pancreatic tissue sample by real time RT-PCR. We also measured PP4 protein levels in in 9 fresh frozen PDA samples and their paired benign pancreatic tissues by Western blot. Using univariate and multivariate analysis, we correlated PP4 expression with survival and other clinicopathologic features. Results: PP4 was overexpressed in 75 of 133 (56%) stage II PDA samples by immunohistochemistry. Compared to benign pancreatic tissue, PP4 protein levels were higher in 9 of 9 PDA samples by Western blot analysis. PP4 mRNA expression levels in PDA samples were significantly higher than benign pancreatic tissue, suggesting that overexpression of PP4 in PDA is due to increase mRNA expression. PP4 overexpression was associated with higher frequencies of distant metastasis (p=0.02) and poor overall and recurrence-free survivals (p = 0.002 and 0.005) independent of tumor size, margin status, and lymph node status (stage) in patients with stage II PDAs. Conclusions: Our study shows that PP4 is frequently overexpressed in PDA samples and is associated with poor prognosis in patients with stage II PDA. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5527. doi:1538-7445.AM2012-5527