Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

Oncotarget. 2015 Jun 30;6(18):16437-48. doi: 10.18632/oncotarget.4103.

Abstract

Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.

Keywords: ALDH1; cancer stem-like cell; ovarian cancer; predictive marker; prognostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aldehyde Dehydrogenase 1 Family
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism
  • Bridged-Ring Compounds / therapeutic use
  • CD24 Antigen / metabolism
  • Drug Resistance, Neoplasm*
  • Female
  • Glycoproteins / metabolism
  • Humans
  • Isoenzymes / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology*
  • Peptides / metabolism
  • Platinum Compounds / therapeutic use
  • Proto-Oncogene Proteins c-kit / metabolism
  • Retinal Dehydrogenase / metabolism*
  • Retrospective Studies
  • Taxoids / therapeutic use
  • Treatment Outcome
  • Tumor Stem Cell Assay

Substances

  • AC133 Antigen
  • Antigens, CD
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • CD24 Antigen
  • CD24 protein, human
  • Glycoproteins
  • Isoenzymes
  • PROM1 protein, human
  • Peptides
  • Platinum Compounds
  • Taxoids
  • taxane
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • Proto-Oncogene Proteins c-kit