Christina A Wicker1, Vinita Takiar1, Rangaswamy Suganya2, Susanne M Arnold3, Yolanda M Brill4, Li Chen3, Craig M Horbinski5, Dana Napier6, Joseph Valentino7, Mahesh R Kudrimoti8, Guoqiang Yu9, Tadahide Izumi10. 1. Department of Radiation Oncology, University of Cincinnati, Cincinnati, OH, United States. 2. Houston Eye Associates, Clinical Research Department, Houston, TX, United States. 3. Department of Internal Medicine, University of Kentucky, Lexington, KY, United States; Markey Cancer Center, University of Kentucky, Lexington, KY, United States. 4. Department of Pathology, University of Kentucky, Lexington, KY, United States. 5. Department of Pathology, Northwestern University, Chicago, IL, United States. 6. Markey Cancer Center, University of Kentucky, Lexington, KY, United States. 7. Department of Otolaryngology, University of Kentucky, Lexington, KY, United States. 8. Department of Radiation Medicine, University of Kentucky, Lexington, KY, United States. 9. F. Joseph Halcomb III M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States. 10. Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, United States. Electronic address: t.izumi@uky.edu.
Abstract
OBJECTIVES: Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). MATERIALS AND METHODS: Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. RESULTS: APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p = 0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p < 0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p = 0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p < 0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p < 0.05). CONCLUSIONS: The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.
OBJECTIVES: Recurrence rates for head and neck squamous cell carcinoma (HNSCC) approach 50% at 5 years. Current staging fails to identify patients with a worse prognosis who might benefit from intensified treatment, which warrants improved prognostic biomarkers. The purpose of this retrospective case study is to identify potential prognostic biomarkers in patients with HNSCC including APE1 (DNA repair/redox gene regulator), NRF2 and PPARGC1A (redox gene regulators), SOD3 and DCN (antioxidant proteins). MATERIALS AND METHODS: Differential protein expression between benign, carcinoma in situ (CIS), and invasive HNSCC tissue specimens from 77 patients was assessed using immunohistochemistry. Protein expression was analyzed with multivariate, pair-wise, and Kaplan-Meier survival analyses to identify potential prognostic biomarkers. Utilizing The Cancer Genome Atlas's transcriptome database, pair-wise and survival analysis was performed to identify potential prognostic biomarkers. RESULTS:APE1, NRF2, PPARGC1A, SOD3, and DCN expression in HNSCC in relation to, lymph node invasion, and patient survival were examined. Elevated APE1 protein expression in CIS corresponded with reduced survival (p = 0.0243). Increased APE1 gene expression in stage T4a HNSCC was associated with reduced patient survival (p < 0.015). Increased PPARGC1A in invasive tumor correlated with reduced survival (p = 0.0281). Patients with lymph node invasion at diagnosis had significantly increased APE1 protein in the primary sites (p < 0.05). Patients with poorly differentiated invasive tumors had reduced PPARGC1A in CIS proximal to the invasive tumor and had elevated DCN and SOD3 in proximal benign tissue (p < 0.05). CONCLUSIONS: The expression of APE1, DCN, and SOD3 is a potential prognostic signature that identifies patients with worsened survival.
Keywords:
Biomarkers; Carcinoma in situ; Immunohistochemistry; Lymph nodes; Retrospective studies; Squamous cell carcinoma of head and neck; Survival analysis; Transcriptome
Authors: Jenny Jaeeun Ko; Alexander C Klimowicz; Amanda Jagdis; Tien Phan; Janessa Laskin; Harold Y Lau; Jodi E Siever; Stephanie K Petrillo; Thomas A Thomson; M Sarah Rose; Gwyn Bebb; Anthony M Magliocco; Desirée Hao Journal: Head Neck Date: 2015-06-29 Impact factor: 3.147