Overexpression of glutathione peroxidase 1 predicts poor prognosis in oral squamous cell carcinoma

J Cancer Res Clin Oncol. 2017 Nov;143(11):2257-2265. doi: 10.1007/s00432-017-2466-7. Epub 2017 Jun 26.

Abstract

Purpose: Intracellular antioxidant enzymes are commonly upregulated in various cancer types and are associated with treatment outcomes. Because the relationship has rarely been examined in oral squamous cell carcinoma (OSCC), we aimed to evaluate the association between the levels of glutathione peroxidase (GPX)1, GPX4, and thioredoxin reductase (TrxR)1 expression and prognosis in patients with OSCC who underwent curative surgical resection.

Methods: This study included 233 patients who underwent curative surgery for previously untreated OSCC between 2000 and 2012. Tumour GPX1, GPX4, and TrxR1 expression was evaluated by immunohistochemistry and was dichotomised to low and high values according to defined expression levels. The association between GPX1, GPX4, and TrxR1 expression and clinicopathological results was analysed. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables.

Results: High GPX1, GPX4, and TrxR1 expression was observed in 99 (42.5%), 133 (57.1%), and 46 (19.7%) patients, respectively. GPX1 overexpression was significantly correlated with nodal metastasis, advanced overall stage, depth of invasion of >10 mm, high grade and perineural invasion (P < 0.05). High GPX4 expression was also related to nodal metastasis, overall advanced stage and high grade (P < 0.05). Univariate and multivariate analyses showed that increased GPX1 expression was significantly associated with poor disease-free, cancer-specific and overall survival (all P < 0.05), while increased GPX4 or TrxR1 expression was not (all P > 0.1).

Conclusions: Tumour GPX1 expression is a useful biomarker predictive of recurrence and survival in OSCC patients.

Keywords: Biomarker; Glutathione peroxidase; Oral squamous cell carcinoma; Recurrence; Survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Female
  • Follow-Up Studies
  • Glutathione Peroxidase / metabolism*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Prognosis
  • Survival Rate
  • Thioredoxin Reductase 1 / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • glutathione peroxidase GPX1
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase
  • TXNRD1 protein, human
  • Thioredoxin Reductase 1