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

doi:10.1371/journal.pone.0102112

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

Research output: Contribution to journal › Article

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 language	English (US)
Article number	e102112
Journal	PloS one
Volume	9
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0102112
State	Published - Jul 14 2014
Externally published	Yes

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ASJC Scopus subject areas

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

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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

DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer. / Lim Seiwert, Tanguy; Wang, Xiao Zhe; Heitmann, Jana; Villegas-Bergazzi, Vivian; Sprott, Kam; Finn, Stephen; O'Regan, Esther; Farrow, Allan D.; Weichselbaum, Ralph R.; Lingen, Mark W.; Cohen, Ezra E.W.; Stenson, Kerstin; Weaver, David T.; Vokes, Everett E.

In: PloS one, Vol. 9, No. 7, e102112, 14.07.2014.

Research output: Contribution to journal › Article

Lim Seiwert, T, Wang, XZ, Heitmann, J, Villegas-Bergazzi, V, Sprott, K, Finn, S, O'Regan, E, Farrow, AD, Weichselbaum, RR, Lingen, MW, Cohen, EEW, Stenson, K, Weaver, DT & Vokes, EE 2014, 'DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer', PloS one, vol. 9, no. 7, e102112. https://doi.org/10.1371/journal.pone.0102112

Lim Seiwert, Tanguy ; Wang, Xiao Zhe ; Heitmann, Jana ; Villegas-Bergazzi, Vivian ; Sprott, Kam ; Finn, Stephen ; O'Regan, Esther ; Farrow, Allan D. ; Weichselbaum, Ralph R. ; Lingen, Mark W. ; Cohen, Ezra E.W. ; Stenson, Kerstin ; Weaver, David T. ; Vokes, Everett E. / DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer. In: PloS one. 2014 ; Vol. 9, No. 7.

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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.",

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

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AU - Lim Seiwert, Tanguy

AU - Wang, Xiao Zhe

AU - Heitmann, Jana

AU - Villegas-Bergazzi, Vivian

AU - Sprott, Kam

AU - Finn, Stephen

AU - O'Regan, Esther

AU - Farrow, Allan D.

AU - Weichselbaum, Ralph R.

AU - Lingen, Mark W.

AU - Cohen, Ezra E.W.

AU - Stenson, Kerstin

AU - Weaver, David T.

AU - Vokes, Everett E.

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N2 - 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.

AB - 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.

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