The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial-like head and neck carcinoma subtypes

Head Neck. 2019 Jun;41(6):1830-1845. doi: 10.1002/hed.25623. Epub 2019 Jan 16.

Abstract

Background: We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial-like (EL) or mesenchymal-like (ML) phenotypes.

Materials and methods: We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival.

Results: EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93-gene expression signature between ML and EL cells was used to build a three-gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA-seq data of the TCGA-HNSC project. Its prognostic value was confirmed in two independent cohorts.

Conclusion: EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.

Keywords: EFS; GPX2; SPRR1A; epithelial-like; gene-expression profile; head and neck cancer; mesenchymal-like; prognosis; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cetuximab / therapeutic use
  • Cisplatin / therapeutic use
  • Cohort Studies
  • Cornified Envelope Proline-Rich Proteins / genetics*
  • Cornified Envelope Proline-Rich Proteins / metabolism
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase / metabolism
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Mice
  • RNA, Messenger / metabolism
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Cornified Envelope Proline-Rich Proteins
  • EFS protein, human
  • RNA, Messenger
  • SPRR1A protein, human
  • GPX2 protein, human
  • Glutathione Peroxidase
  • Cetuximab
  • Cisplatin