Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer

Br J Cancer. 2014 Jun 10;110(12):2935-44. doi: 10.1038/bjc.2014.226. Epub 2014 May 1.

Abstract

Background: Tumour aggressiveness might be related to the degree of main cancer hallmark acquirement of tumour cells, reflected by expression levels of specific biomarkers. We investigated the expression of Aldh1, Survivin, and EpCAM, together reflecting main cancer hallmarks, in relation to clinical outcome of colorectal cancer (CRC) patients.

Methods: Immunohistochemistry was performed using a tumour tissue microarray of TNM (Tumour, Node, Metastasis)-stage I-IV CRC tissues. Single-marker expression or their combination was assessed for associations with the clinical outcome of CRC patients (N=309).

Results: Increased expression of Aldh1 or Survivin, or decreased expression of EpCAM was each associated with poor clinical outcome, and was therefore identified as clinically unfavourable expression. Analyses of the combination of all three markers showed worse clinical outcome, specifically in colon cancer patients, with an increasing number of markers showing unfavourable expression. Hazard ratios ranged up to 8.3 for overall survival (P<0.001), 36.6 for disease-specific survival (P<0.001), and 27.1 for distant recurrence-free survival (P<0.001).

Conclusions: Our data identified combined expression levels of Aldh1, Survivin, and EpCAM as strong independent prognostic factors, with high hazard ratios, for survival and tumour recurrence in colon cancer patients, and therefore reflect tumour aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase 1 Family
  • Antigens, Neoplasm / biosynthesis*
  • Biomarkers, Tumor / biosynthesis*
  • Cell Adhesion Molecules / biosynthesis*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Epithelial Cell Adhesion Molecule
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Isoenzymes / biosynthesis*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Retinal Dehydrogenase / biosynthesis*
  • Survivin
  • Tissue Array Analysis

Substances

  • Antigens, Neoplasm
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Inhibitor of Apoptosis Proteins
  • Isoenzymes
  • Survivin
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase