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PLoS One ; 9(7): e102112, 2014.
Article in English | MEDLINE | ID: mdl-25019640

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.


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