Expression of xCT as a predictor of disease recurrence in patients with colorectal cancer

Anticancer Res. 2015 Feb;35(2):677-82.

Abstract

Background: The function of a cysteine-glutamate exchanger (xCT) transporter is to increase the intracellular concentration of glutathione in order to protect cells from oxidative stress. In several types of cancer, xCT is thought to play a role in the onset of resistance to chemotherapy and radiotherapy. xCT is stabilized on the tumor cell surface after combining with cluster of differentiation 44 variant (CD44v).

Materials and methods: We examined the xCT and CD44v6 expression in 304 primary tumor samples obtained from patients with colorectal cancer using immunohistochemical analysis.

Results: Immunoreactivity for xCT was observed in 208 (68.4%) tumors. Among 218 patients with stage I-III disease who underwent curative surgery, the postoperative recurrence rate was 32.9% in those with xCT-positive tumors, which was significantly (p=0.003) higher than in those with xCT-negative tumors (10.7%). Immunoreactivity for CD44v6 was observed in 101 cases (33.2%), although the rate of postoperative recurrence in patients with CD44v6-positive tumors did not exhibit any significant correlation. Multivariate analyses revealed increased xCT expression to be an independent significant predictor of disease recurrence, in addition to depth of tumor invasion, lymph node metastasis and venous invasion.

Keywords: CD44v6; CRC; colorectal cancer; immunohistochemistry; recurrence; xCT.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Cysteine / metabolism*
  • Female
  • Glutamic Acid / metabolism*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • CD44v6 antigen
  • Hyaluronan Receptors
  • Glutamic Acid
  • Cysteine