ALDH1 is an independent prognostic factor for patients with stages II-III rectal cancer after receiving radiochemotherapy

Br J Cancer. 2014 Jan 21;110(2):430-4. doi: 10.1038/bjc.2013.767. Epub 2013 Dec 10.

Abstract

Background: About one in five patients with locally advanced rectal cancer (RC) suffers recurrence or distant metastasis after neoadjuvant therapy. We investigated how cancer stem cell markers change after neoadjuvant therapy and how these markers relate to recurrence.

Methods: Pretreatment biopsies and postoperative specimens were taken from 64 patients with locally advanced rectal adenocarcinoma who received preoperative radiochemotherapy (RCT) between sampling. Samples were tested immunohistochemically for CD44, LGR5, ALDH1 and CD166; scores were dichotomised as high or low. The median follow-up period was 36 months.

Results: High expression of CD44, LGR5, ALDH and CD166 was found in 38%, 5%, 48% and 10%, respectively, before RCT and 86%, 33%, 71% and 52%, respectively, after RCT. CD44 (P=0.001), LGR5 (P=0.049) and CD166 (P=0.003) were significantly upregulated after RCT. Whereas no recurrence was seen during the follow-up in the low ALDH group, 40% of the high ALDH group suffered recurrence. In multivariate COX analysis, postoperative ALDH1 independently predicted poor prognosis in patients with RC who received RCT (P=0.0095).

Conclusion: Preoperative RCT upregulates expression of stem cell markers in patients with RC. High post-treatment ALDH1 expression predicts poor prognosis for these patients after neoadjuvant therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase 1 Family
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / genetics
  • Chemoradiotherapy / methods
  • Female
  • Fetal Proteins / biosynthesis
  • Fetal Proteins / genetics
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronan Receptors / genetics
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / radiotherapy
  • Neoplasm Staging
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects
  • Prognosis
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / genetics
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / enzymology*
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / radiotherapy
  • Retinal Dehydrogenase / biosynthesis*
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Young Adult

Substances

  • ALCAM protein, human
  • Antigens, CD
  • Biomarkers, Tumor
  • CD44 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • Hyaluronan Receptors
  • Isoenzymes
  • LGR5 protein, human
  • Receptors, G-Protein-Coupled
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase