DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer

PLoS One. 2014 Jul 14;9(7):e102112. doi: 10.1371/journal.pone.0102112. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • DNA Repair / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Knockout Techniques
  • HeLa Cells
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Induction Chemotherapy / methods
  • Induction Chemotherapy / standards*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Precision Medicine / methods
  • Protein Serine-Threonine Kinases / metabolism*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • xeroderma pigmentosum group F protein
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases