Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma

Purpose: Protein phosphatase 4 (PP4) has been reported to be overexpressed in breast and lung cancers. PP4 plays an important role in the regulation of centrosome maturation, DNA repair, NF-κB, and c-jun-NH2-kinase (JNK) signaling pathways. However, the expression and functions of PP4 in pancreatic cancer have not been studied. Experimental Design: We examined the expression of PP4 catalytic subunit (PP4C) protein in 133 patients with stage II pancreatic ductal adenocarcinoma (PDAC) and their paired benign pancreatic samples (N = 113) by immunohistochemistry. To confirm the immunohistochemical results, we measured PP4C protein and mRNA levels by Western blotting and real-time reverse transcriptase PCR. Using univariate and multivariate analysis, we correlated PP4C expression with survival and other clinicopathologic features. Results: PP4C was overexpressed in 75 of 133 (56.4%) stage II PDAC samples, which was significantly higher than the paired benign pancreatic tissue (15%, 17 of 113). PP4C mRNA expression levels were also higher in PDAC samples than the paired benign pancreatic tissue. Overexpression of PP4C in PDAC samples was associated with higher frequencies of distant metastasis (P = 0.02) and poor disease-free and overall survivals in patients with stage II PDAC (P = 0.006 and 0.02) independent of tumor size, margin status, and lymph node status (stage). Conclusions: Our study showed that PP4C is overexpressed in PDAC. Overexpression of PP4C in PDAC samples is associated with poor prognosis in patients with stage II PDAC. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDAC. Impact: Our study showed that PP4C is an independent prognostic factor in patients with stage II PDAC.