Synergistic role between p53 and JWA: prognostic and predictive biomarkers in gastric cancer

PLoS One. 2012;7(12):e52348. doi: 10.1371/journal.pone.0052348. Epub 2012 Dec 21.

Abstract

Expression of p53 appears to be correlated to prognosis in patients with malignancy, but its role in gastric carcinoma has remained controversial. Recently we reported that JWA, an ADP-ribosylation-like factor 6 interacting protein 5 (ARL6ip5), was both prognostic for overall survival and predictive for platinum-based treatment of gastric cancer. In this study, we aimed to investigate p53 expression as a prognostic and predictive marker in resectable gastric cancer, alone and in combination with JWA. Expression of p53 was examined in three large patient cohorts (total n=1155) of gastric cancer. High expression of p53 was significantly correlated with unfavorable clinicopathologic parameters and decreased overall patient survival. Furthermore, patients with high p53 expression in tumors acquired remarkable survival benefit from adjuvant first-line platinum-based-chemotherapy. The synergy between p53 and JWA in predicting patient outcome was demonstrated, while no significantly elevated predictive value concerning chemotherapy was observed. Thus, p53 expression is a potent prognostic and predictive factor for resectable gastric cancer with adjuvant platinum-based chemotherapy. A combined effect of p53 with JWA as efficient prognostic indicators was found for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Female
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Transport Proteins
  • Stomach Neoplasms / metabolism*
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • ARL6IP5 protein, human
  • Biomarkers, Tumor
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Transport Proteins
  • Tumor Suppressor Protein p53

Grants and funding

This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions (http://jsycw.ec.js.edu.cn); the National Natural Science Foundation of China (30930080 and 81110027) (http://www.nsfc.gov.cn); the Foundation of Cancer Center of Nanjing Medical University (08ZLKF08) (http://202.195.178.127/zlsys). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.