Overexpression of PODXL/ITGB1 and BCL7B/ITGB1 accurately predicts unfavorable prognosis compared to the TNM staging system in postoperative pancreatic cancer patients

PLoS One. 2019 Jun 5;14(6):e0217920. doi: 10.1371/journal.pone.0217920. eCollection 2019.

Abstract

We previously reported that overexpression of PODXL, BCL7B, and ARHGEF4 in pancreatic cancer tissue is correlated with pancreatic cancer-related survival. The aim of this study was to investigate the use of PODXL, BCL7B, ARHGEF4, and the integrin family member ITGB1 as useful markers for the prognosis of postoperative pancreatic cancer patients in comparison with tumor size and the tumor node metastasis (TNM) staging system. Immunohistochemistry was performed using an anti-ITGB1 antibody on 102 samples of pancreatic cancer tissue surgically resected at the University of Kochi Medical School Hospital and the Matsuyama Shimin Hospital. Univariate Cox proportional hazards regression analysis showed that TNM stage and overexpression of PODXL, BCL7B, and ITGB1 were correlated with postoperative survival. However, tumor size was not significantly associated with postoperative prognosis of pancreatic cancer compared to these features. Multivariate Cox proportional hazards regression analysis showed that the overexpression of both PODXL and ITGB1 and overexpression of both BCL7B and ITGB1 increased the hazard ratio (6.27, 95% confidence interval [CI] 2.58-15.21; and 3.93, 95% CI 1.74-8.91, respectively) compared to that of TNM stage (IIA and IIB vs. III and IV; 3.05, 95% CI 1.25-7.42). These results imply that the combination of PODXL with ITGB1 and the combination of BCL7B with ITGB1 accurately predicted the postoperative outcomes of pancreatic cancer patients, and they were superior compared to the TNM staging system. The combination of PODXL with ITGB1 would be particularly useful, as it was the most highly correlated with postoperative outcomes. Importantly, the present results are useful to determine which adjuvant therapy should be selected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Integrin beta1 / metabolism*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Postoperative Period
  • Prognosis
  • Proportional Hazards Models
  • Proteins / metabolism*
  • Rho Guanine Nucleotide Exchange Factors / metabolism
  • Sialoglycoproteins / metabolism*
  • Treatment Outcome
  • Tumor Burden

Substances

  • ARHGEF4 protein, human
  • BCL7B protein, human
  • Integrin beta1
  • Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • Sialoglycoproteins
  • podocalyxin

Grants and funding

This research was supported by the Grants-in-Aid for Scientific Research (KAKENHI; 24591013, 15K14396, and 17K09463 to KT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.