Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients. (December 2020)

• Record Type: Journal Article
• Authors: Wicker, Christina A.; Takiar, Vinita; Suganya, Rangaswamy; Arnold, Susanne M.; Brill, Yolanda M.; Chen, Li; Horbinski, Craig M.; Napier, Dana; Valentino, Joseph; Kudrimoti, Mahesh R.; Yu, Guoqiang; Izumi, Tadahide
• Is Part Of: Oral oncology. Volume 111(2020)
• Publication Date: 2020-12
• Subjects: Squamous cell carcinoma of head and neck -- Biomarkers -- Survival analysis -- Lymph nodes -- Carcinoma in situ -- Immunohistochemistry -- Retrospective studies -- Transcriptome; HNSCC head and neck squamous cell carcinoma -- APE1 apurinic/apyrimidinic endonuclease 1 -- DCN decorin -- SOD3 superoxide dismutase 3 -- NRF2 nuclear factor erythroid 2 like 2 -- PPARGC1A peroxisome proliferator-activated receptor gamma coactivator -- CIS carcinoma in situ -- LR Log rank -- GW Gehan-Wilcoxon; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2020.104949
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: APE1 and PPARGC1A protein levels associated with decreased survival. Higher APE1 gene expression in stage T4a HNSCC linked to reduced survival. Increased APE1 protein was linked to presence of lymph node invasion. Low PPARGC1A in tumor-adjacent CIS linked to poorly differentiated invasive HNSCC. High DCN and SOD3 protein linked to poorly differentiated invasive HNSCC. 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.