title: CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.
abstract: OBJECTIVE
  Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype.
  
  
  METHODS
  101 EC patients treated with nCRT and surgery were included. Sufficient pre-treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group.
  
  
  RESULTS
  Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed.
  
  
  CONCLUSIONS
  Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT.
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Honing
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Kirill V
authors.initials: KV
authors.lastname: Pavlov
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Véronique E M
authors.initials: VE
authors.lastname: Mul
authors.affiliation: Department of Pathology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Karrenbeld
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Coby
authors.initials: C
authors.lastname: Meijer
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Faiz
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Smit
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Geke A P
authors.initials: GA
authors.lastname: Hospers
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Johannes G M
authors.initials: JG
authors.lastname: Burgerhof
authors.affiliation: Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Frank A E
authors.initials: FA
authors.lastname: Kruyt
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: j.t.m.plukker@umcg.nl.
authors.forename: John T M
authors.initials: JT
authors.lastname: Plukker
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D053823:Hedgehog Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; C509239:SHH protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Cancer; Chemoradiotherapy; Esophageal; Neoadjuvant; Stem cell biomarkers