title: DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.
abstract: BACKGROUND
  Induction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.
  
  
  METHODS
  Expression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.
  
  
  RESULTS
  We found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.
  
  
  CONCLUSIONS
  We identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois, United States of America; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: XiaoZhe
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Jana
authors.initials: J
authors.lastname: Heitmann
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: Vivian
authors.initials: V
authors.lastname: Villegas-Bergazzi
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: Kam
authors.initials: K
authors.lastname: Sprott
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: Esther
authors.initials: E
authors.lastname: O'Regan
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Farrow
authors.affiliation: Department of Radiation Oncology, The University of Chicago, Chicago, Illinois, United States of America; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois, United States of America; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.affiliation: Department of Surgery, Section of Head and Neck Surgery, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Stenson
authors.affiliation: On-Q-ity Inc., Waltham, Massachusetts, United States of America.
authors.forename: David T
authors.initials: DT
authors.lastname: Weaver
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois, United States of America; The University of Chicago Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D060828:Induction Chemotherapy / Q000379:methods / Q000592:standards*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D057285:Precision Medicine / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C095888:xeroderma pigmentosum group F protein