Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

Kapo Saukkonen,Olle Nilsson,Anne Juuti,Christian Fermér,Harri Mustonen,Jaana Hagström,Hanna Seppänen,Stig Nordling,Caj Haglund,Francisco X Real

doi:10.1371/journal.pone.0129012

Kapo Saukkonen, Olle Nilsson + Show 8 more

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https://doi.org/10.1371/journal.pone.0129012

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Abstract

Aim of the StudyPodocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.Patients and MaterialsWith tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associa-tions of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher’s exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier anal-ysis and the Cox proportional hazard model.ResultsThe polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0%) specimens and the monoclonal antibody was highly expressed in 36 (21.8%) cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045) and perineural invasion (p=0.005), and high expression by the mono-clonal antibody with poor differentiation (p=0.033). High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR) = 1.62; 95% confidence interval (CI) 1.12-2.33; p=0.01) and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001). The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%), and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001).ConclusionWe found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value.

Highlights

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is extremely poor, with overall 5-year survival less than 5% [1,2]
High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR) = 1.62; 95% confidence interval (CI) 1.12-2.33; p=0.01) and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p
The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (/< 20%), and perivascular invasion

Summary

Introduction

The prognosis of pancreatic ductal adenocarcinoma (PDAC) is extremely poor, with overall 5-year survival less than 5% [1,2]. Finland has about 1000 new cases per year, and PDAC is the third leading cause of cancer-related death [1]. In the United States, PDAC is the fourth leading cause of cancer-related mortality, causing annually about 40,000 deaths [2]. The survival rate has not improved markedly over the last few decades [2]. Overall survival is poor, there is a great variation between patients of the same stage, for whom new biomarkers might help in predicting prognosis. Research on potential biomarkers has been intense, but it still lacks good prognostic markers [4,5,6]

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