Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

J Exp Clin Cancer Res. 2012 Sep 11;31(1):71. doi: 10.1186/1756-9966-31-71.

Abstract

Background: Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers.

Methods: Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated.

Results: Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0-80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival.Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003).

Conclusions: Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Aged
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / metabolism
  • Colonic Neoplasms* / pathology
  • Colonic Neoplasms* / therapy
  • Disease-Free Survival
  • Dystroglycans* / genetics
  • Dystroglycans* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins* / genetics
  • Glycoproteins* / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Peptides* / genetics
  • Peptides* / metabolism
  • Prognosis
  • Treatment Outcome

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Dystroglycans