Clinical implication of Pin1 expression in pancreatic ductal adenocarcinoma

Abstract

Purpose: The prognosis of pancreatic ductal adenocarcinoma (PDAC) is poor even after curative surgical resection. Therefore, discovering new important factors controlling PDAC progression is essential. Pin1 overexpression is seen in several malignancies and is reported to promote tumor progression through activation of transcriptional factors such as NF-kappaB, STAT3, and FOXC1. However, no reports have focused on the expression levels of Pin1 in PDAC. Therefore, we thought to evaluate Pin1 expression in PDAC, investigate the correlations with clinicopathological variables, and determine whether Pin1 is a promising therapeutic target in PDAC patients. Experimental Design: The expression levels of Pin1 and related factors were evaluated by immunohistochemical staining. Moreover, the relationship between Pin1 expression and clinicopathological features or prognosis in 120 PDAC patients were investigated. Results: Pin1 expression was increased in some cases of PDAC, and was associated with vascular invasion in PDAC. The univariate and multivariate analyses revealed that high Pin1 expression in PDAC was an independent factor for poor prognosis. Pin1 enhanced activation of transcriptional factors such as STAT3 and FOXC1, resulted in aggressive tumor progression. Increased Pin1 expression induced tumor growth by accelerating cell proliferation and inhibiting cell apoptosis. Moreover, Pin1 overexpression promoted tumor invasion by enhancing EMT. As these results, the incidence of hematogenous recurrence was significantly higher in PDAC with high Pin1 expression. Conclusions: Pin1 overexpression is associated with aggressive tumor progression and poor prognosis in PDAC; therefore, Pin1 is an excellent biomarker for predicting its malignant status and is a promising therapeutic target in patients with PDAC.