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DNA repair biomarker profiling of head and neck cancer: Ku80 expression predicts locoregional failure and death following radiotherapy.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Moeller, Benjamin J. Yordy, John S. Williams, Michelle D. Giri, Uma Raju, Uma Shankar Molkentine, David P. Byers, Lauren A. Heymach, John V. Story, Michael D. Lee, Julie J. Sturgis, Erich M. Schuller, David E. Garden, Adam Seth Ang, Kuan Kee Schwartz, David Lee |
| Copyright Year | 2011 |
| Abstract | PURPOSE Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes. 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. |
| Starting Page | 544 |
| Ending Page | 544 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/early/2011/03/25/1078-0432.CCR-10-2641.full.pdf |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/17/7/2035.full.pdf |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/early/2011/02/24/1078-0432.CCR-10-2641.full.pdf |
| PubMed reference number | 21349997v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/1078-0432.CCR-10-2641 |
| DOI | 10.1158/1078-0432.ccr-10-2641 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Volume Number | 17 |
| Issue Number | 7 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Biological Markers Cessation of life DNA Repair Eighty Nine Liver Failure, Acute Neoplasms Non-Small Cell Lung Carcinoma Patients Specimen Squamous Epithelial Cells Squamous cell carcinoma of the head and neck Tissue Microarray XRCC5 wt Allele |
| Content Type | Text |
| Resource Type | Article |
