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

Tanguy Lim Seiwert, Xiao Zhe Wang, Jana Heitmann, Vivian Villegas-Bergazzi, Kam Sprott, Stephen Finn, Esther O'Regan, Allan D. Farrow, Ralph R. Weichselbaum, Mark W. Lingen, Ezra E.W. Cohen, Kerstin Stenson, David T. Weaver, Everett E. Vokes

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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.

Original languageEnglish (US)
Article numbere102112
JournalPloS one
Volume9
Issue number7
DOIs
StatePublished - Jul 14 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lim Seiwert, T., Wang, X. Z., Heitmann, J., Villegas-Bergazzi, V., Sprott, K., Finn, S., O'Regan, E., Farrow, A. D., Weichselbaum, R. R., Lingen, M. W., Cohen, E. E. W., Stenson, K., Weaver, D. T., & Vokes, E. E. (2014). DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer. PloS one, 9(7), [e102112]. https://doi.org/10.1371/journal.pone.0102112