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. 2012 Aug;21(8):1336-43.
doi: 10.1158/1055-9965.EPI-12-0223. Epub 2012 Jun 4.

Overexpression of Protein Phosphatase 4 Correlates With Poor Prognosis in Patients With Stage II Pancreatic Ductal Adenocarcinoma

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Overexpression of Protein Phosphatase 4 Correlates With Poor Prognosis in Patients With Stage II Pancreatic Ductal Adenocarcinoma

Shaofan Weng et al. Cancer Epidemiol Biomarkers Prev. .
Free PMC article

Abstract

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-NH(2)-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.

Figures

Figure 1
Figure 1
Representative micrographs show PP4C expression in pancreatic ductal adenocarcinoma (PDAC) samples and benign pancreatic tissue. A and B, strong cytoplasmic and nuclear staining for PP4C in a moderately to poorly differentiated PDAC; C and D, a moderately differentiated PDAC with weak staining for PP4C; E and F, Representative benign pancreatic tissue that is negative for PP4C (Original magnification, 40× for A, C, and E; 200× for B, D, and F).
Figure 2
Figure 2
PP4C is overexpressed in pancreatic ductal adenocarcinoma (PDAC). A, Immunohistochemical staining results for PP4C expression in PDAC (N=133) and their paired benign pancreatic tissue samples (N=113). The expression of PP4C is significantly higher in PDAC samples than their paired benign pancreatic tissue (P<0.0001). B. 150 μg of cell lysates from each of 9 PDAC samples and their matched benign pancreatic tissue samples were resolved by 10% SDS-PAGE and immunoblotted with anti-PP4C or anti-GAPDH as loading control. C. Bar-graph showing the relative PP4C mRNA expression levels in benign pancreatic tissue samples and PDAC samples measured by real time QRT-PCR. Relative PP4C mRNA expression levels that were normalized by RPS6 mRNA levels (internal control) were plotted. PP4C mRNA was overexpressed in PDAC samples compared to the benign pancreatic tissue samples. The experiments were repeated three times.
Figure 3
Figure 3
Kaplan-Meier curves for disease-free survival (A) and overall survival (B) by PP4C expression levels in patients with stage II PDAC.

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