Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma

PLoS One. 2015 Jun 8;10(6):e0129012. doi: 10.1371/journal.pone.0129012. eCollection 2015.

Abstract

Aim of the study: Podocalyxin-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 materials: With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associations 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 analysis and the Cox proportional hazard model.

Results: The 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).

Conclusion: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / pathology
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Sialoglycoproteins
  • podocalyxin

Grants and funding

This study was supported by grants from Sigrid Juselius Foundation, Finska Läkaresällskapet, Liv och Hälsa, Kurt och Doris Palander Foundation and K Albin Johansson Foundation. Fujirebio Diagnostics AB and Onson Consulting provided support in the form of salaries for authors CF and ON, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.