Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy

Br J Cancer. 2014 Jan 21;110(2):421-9. doi: 10.1038/bjc.2013.712. Epub 2013 Dec 3.

Abstract

Background: DAP3 is a member of the death-associated protein (DAP) family and is characterised by proapoptotic function. It is involved in both exogenous and endogenous apoptotic pathways. In our previous studies, apoptotic level was found to be correlated with the effectiveness of preoperative chemotherapy. The effectiveness of preoperative chemotherapy was also associated with the overall effectiveness of the combined therapy and prognosis. The present study aimed to investigate the role of DAP3 in the evaluation of preoperative chemotherapy effectiveness and its ability to predict prognosis in gastric cancer.

Methods: Quantitative PCR and immunohistochemistry staining were performed in 87 patients who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer cell lines to investigate its impact on cell growth, migration, adhesion and invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis and caspase-3.

Results: Higher DAP3 expression in gastric tumours was correlated with better prognosis. Knockdown of DAP3 expression promoted cell migration and enhanced resistance to chemotherapy by inhibiting apoptosis.

Conclusion: DAP3 is a potential molecular marker for response to preoperative chemotherapy and for predicting prognosis in gastric cancer patients treated with neoadjuvant chemotherapy and gastrectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers, Tumor / genetics
  • Caspase 3 / genetics
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Female
  • Fluorouracil / administration & dosage
  • Gastrectomy / methods
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prognosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • DAP protein, human
  • Organoplatinum Compounds
  • Oxaliplatin
  • Caspase 3
  • Fluorouracil