Evaluation of antioxidant network proteins as novel prognostic biomarkers for head and neck cancer patients

Oral Oncol. 2020 Dec:111:104949. doi: 10.1016/j.oraloncology.2020.104949. Epub 2020 Aug 12.

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.

Keywords: Biomarkers; Carcinoma in situ; Immunohistochemistry; Lymph nodes; Retrospective studies; Squamous cell carcinoma of head and neck; Survival analysis; Transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Databases, Genetic
  • Decorin / genetics
  • Decorin / metabolism*
  • Female
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Prognosis
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • DCN protein, human
  • Decorin
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Neoplasm Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • SOD3 protein, human
  • Superoxide Dismutase
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase