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: Tanguy Y Seiwert, XiaoZhe 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
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e102112 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25019640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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