title: Cancer Stem Cell Properties as Factors Predictive of Chemoresistance in Neoadjuvantly-treated Patients with Ovarian Cancer.
abstract: OBJECTIVE
  The nuclear factor erytheroid 2-related factor 2-kelch-like ECH-associated protein (NRF2-KEAP1) system and stem cell-like cancer cells are associated with platinum resistance in ovarian cancer. Our objective was to investigate the possible association between platinum resistance, cellular redox-state regulation and stem cell properties in ovarian cancer.
  
  
  METHODS
  Thirty-eight patients with epithelial ovarian cancer were included. All patients had undergone primary diagnostic laparoscopy, platinum-based neoadjuvant chemotherapy, and debulking surgery. Tumor samples were analyzed for NRF2, KEAP1, protein deglycase 1 (DJ1/PARK7), cluster of differentiation molecules 44 (CD44) and 117 (CD117) and aldehyde dehydrogenase 1 (ALDH1) by immunohistochemistry.
  
  
  RESULTS
  Positive pre-treatment expression of CD44 (p=0.013) and stable/increased post-therapy CD44 expression were associated with platinum resistance (p=0.001). Negative pre-treatment expression of cytoplasmic ALDH1 predicted sensitivity to platinum (p=0.017). Pre-treatment nuclear KEAP1 expression was greater in stage II-III cancer (p=0.0003). After neoadjuvant treatment, all samples were nuclear KEAP1-positive (p=0.025) and increased nuclear KEAP1 expression was associated with higher tumor stage (p=0.0001).
  
  
  CONCLUSIONS
  CD44 and cytoplasmic ALHD1 could be potential indicators of platinum resistance during neoadjuvant chemotherapy for ovarian cancer.
authors.affiliation: Medical Research Center Oulu, University of Oulu, Oulu, Finland Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland marjo.pylvas-eerola@ppshp.fi.
authors.forename: Marjo
authors.initials: M
authors.lastname: Pylväs-Eerola
authors.affiliation: Medical Research Center Oulu, University of Oulu, Oulu, Finland Department of Pathology, Oulu University Hospital, Oulu, Finland.
authors.forename: Annikki
authors.initials: A
authors.lastname: Liakka
authors.affiliation: Medical Research Center Oulu, University of Oulu, Oulu, Finland Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Puistola
authors.affiliation: Medical Research Center Oulu, University of Oulu, Oulu, Finland Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Koivunen
authors.affiliation: Medical Research Center Oulu, University of Oulu, Oulu, Finland Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala
mesh_terms: D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D010084:Oxidation-Reduction; D050697:Retinal Dehydrogenase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH1; CD44; Cancer stem cell; NRF2; platinum resistance