title: Tumor cells with low proteasome subunit expression predict overall survival in head and neck cancer patients.
abstract: BACKGROUND
  Experimental and clinical data suggest that solid cancers contain treatment-resistant cancer stem cells that will impair treatment efficacy. The objective of this study was to investigate if head and neck squamous cell carcinoma (HNSCC) also contain cancer stem cells that can be identified by low 26S proteasome activity and if their presence correlates to clinical outcome.
  
  
  METHODS
  Human HNSCC cells, engineered to report lack of proteasome activity based on accumulation of a fluorescent fusion protein, were separated based on high (ZsGreen-cODCneg) or low (ZsGreen-cODCpos) proteasome activity. Self-renewal capacity, tumorigenicity and radioresistance were assessed. Proteasome subunit expression was analyzed in tissue microarrays and correlated to survival and locoregional cancer control of 174 patients with HNSCC.
  
  
  RESULTS
  HNSCC cells with low proteasome activity showed a significantly higher self-renewal capacity and increased tumorigenicity. Irradiation enriched for ZsGreen-cODCpos cells. The survival probability of 82 patients treated with definitive radio- or chemo-radiotherapy exhibiting weak, intermediate, or strong proteasome subunit expression were 21.2, 28.8 and 43.8 months (p = 0.05), respectively. Locoregional cancer control was comparably affected.
  
  
  CONCLUSIONS
  Subpopulations of HNSCC display stem cell features that affect patients' tumor control and survival. Evaluating cancer tissue for expression of the proteasome subunit PSMD1 may help identify patients at risk for relapse.
authors.forename: Chann
authors.initials: C
authors.lastname: Lagadec
authors.forename: Erina
authors.initials: E
authors.lastname: Vlashi
authors.forename: Sunita
authors.initials: S
authors.lastname: Bhuta
authors.forename: Chi
authors.initials: C
authors.lastname: Lai
authors.forename: Paul
authors.initials: P
authors.lastname: Mischel
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Michael
authors.initials: M
authors.lastname: Henke
authors.affiliation: Department of Radiation Oncology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA. fpajonk@mednet.ucla.edu.
authors.forename: Frank
authors.initials: F
authors.lastname: Pajonk
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D063868:Patient Outcome Assessment; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease