Abstract | PURPOSE: EXPERIMENTAL DESIGN: Archival HNSCC tumor specimens (n = 89) were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort (n = 34). RESULTS: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy (P < 0.01). The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years. CONCLUSIONS: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment.
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Authors | Benjamin J Moeller, John S Yordy, Michelle D Williams, Uma Giri, Uma Raju, David P Molkentine, Lauren A Byers, John V Heymach, Michael D Story, J Jack Lee, Erich M Sturgis, Randal S Weber, Adam S Garden, K Kian Ang, David L Schwartz |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 17
Issue 7
Pg. 2035-43
(Apr 01 2011)
ISSN: 1557-3265 [Electronic] United States |
PMID | 21349997
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- DNA Helicases
- XRCC5 protein, human
- Ku Autoantigen
- DNA Repair Enzymes
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Alphapapillomavirus
- Biomarkers, Tumor
(metabolism)
- Carcinoma, Squamous Cell
(metabolism, mortality, radiotherapy, virology)
- DNA Breaks, Double-Stranded
- DNA Helicases
(metabolism)
- DNA Repair
- DNA Repair Enzymes
(metabolism)
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Head and Neck Neoplasms
(metabolism, mortality, radiotherapy, virology)
- Humans
- Ku Autoantigen
- Male
- Middle Aged
- Papillomavirus Infections
(complications)
- Protein Array Analysis
- Tumor Cells, Cultured
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