title: The Stem Cell Factor HMGA2 Is Expressed in Non-HPV-Associated Head and Neck Squamous Cell Carcinoma and Predicts Patient Survival of Distinct Subsites.
abstract: The transcription factor high-mobility AT-hook 2 (HMGA2) is involved in stem cell renewal and is expressed in many tumor tissues. Head and neck squamous cell carcinomas (HNSCC) comprise tumors of the upper aerodigestive tract and are characterized by high recurrence rates that represent a challenge to patient management. The study addresses the potential of HMGA2 as a molecular biomarker for HNSCC patient survival.
  
  
  
  Patients with HNSCC of the larynx, pharynx, tonsils, or oral cavity were recruited in a hospital-based case-control study (n = 202). Quantitative expression of HMGA2 in tumor tissues was measured by RT-PCR. In a 6- to 10-year follow-up, secondary cancers, vital status, and cause of death were ascertained. The HR and 95% confidence intervals (CI) for overall, tumor-specific, and progression-free survival were estimated by Cox proportional hazards with HMGA2 expression level as the independent variable.
  
  
  
  High HMGA2 expression in tumor tissues of HNSCC patients was significantly correlated with negative HPV status (P = 0.01), and associated with shorter overall survival time. In Cox regression modeling, HMGA2 expression yielded a risk increase for overall and tumor-specific death in subsets of HNSCC patients, that is, laryngeal cancer patients (overall survival: HR = 4.00; 95% CI, 1.18-13.62) and in oral cancer patients (tumor-specific survival: HR = 2.88; 95% CI, 1.06-7.84), but not in patients with pharyngeal and tonsillar HNSCC.
  
  
  
  HMGA2 expression is associated with a risk increase for adverse outcomes in patients with HNSCC of the larynx and oral cavity.
  
  
  
  The understanding of stem cell signaling in HNSCC may offer new strategies for cancer treatment. Cancer Epidemiol Biomarkers Prev; 26(2); 197-205. ©2016 AACR.
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. kguenth@leibniz-bips.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Günther
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Ronja
authors.initials: R
authors.lastname: Foraita
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Friemel
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Günther
authors.affiliation: Center for Human Genetics (ZHG), University of Bremen, Bremen, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
authors.affiliation: Center for Human Genetics (ZHG), University of Bremen, Bremen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Nimzyk
authors.affiliation: Center for Human Genetics (ZHG), University of Bremen, Bremen, Germany.
authors.forename: Dominique Nadine
authors.initials: DN
authors.lastname: Markowski
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.|Protein Research Unit Ruhr within Europe (PURE), Ruhr-University Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Behrens
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Ahrens
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D005858:Germany / Q000453:epidemiology; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D019089:Stem Cell Factor / Q000096:biosynthesis / Q000235:genetics*; D015996:Survival Rate / Q000639:trends
chemical_list: D004279:DNA, Viral; D025743:HMGA2 Protein; D012334:RNA, Neoplasm; D019089:Stem Cell Factor