Evaluation of the prognostic value and functional roles of CD44v6 in gastric cancer

J Cancer Res Clin Oncol. 2015 Oct;141(10):1809-17. doi: 10.1007/s00432-015-1964-8. Epub 2015 Mar 26.

Abstract

Purpose: Tumor stem cell surface marker CD44v6, a member of the CD44 protein family, is causally involved in the metastasis of cancer. Little is known about the functions of CD44v6 in gastric cancer. The aim of this study was to evaluate the prognostic value of CD44v6 and investigate its functional roles.

Methods: The expression of CD44v6 in 208 primary gastric adenocarcinoma patient samples was examined using immunohistochemistry and its correlation with clinicopathological parameters, and 5-year patient survival was assessed. Two pairs of MGC-803 stable cells with either CD44v6 overexpression or knockdown were created. The effect of CD44v6 on cell proliferation, colony formation, migration and apoptosis was investigated using these two pairs of cells.

Results: Overexpression of CD44v6 was observed in all cancer cell lines. The 5-year survival rate of patients with positive CD44v6 expression is significantly worse compared to those with negative expression (38.8 vs. 73.6 %). CD44v6 and TNM stage are two independent prognostic factors of primary gastric adenocarcinoma. The risk factors for the positive CD44v6 expression are location of tumor, depth of invasion, lymph node metastasis, Lauren classification and TNM stage. In MGC-803 cells, CD44 stimulated proliferation and colony formation, antagonized oxaliplatin-induced apoptosis, but did not affect migration.

Conclusion: CD44v6 is an important prognosis marker in gastric cancer. Tissue specificity may affect the functions of CD44v6, and further work is needed to elucidate its regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Apoptosis / physiology
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Female
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • CD44v6 antigen
  • Hyaluronan Receptors