Identification of new candidate therapeutic target genes in head and neck squamous cell carcinomas

Oncotarget. 2016 Jul 26;7(30):47418-47430. doi: 10.18632/oncotarget.10163.

Abstract

Background: We aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance.

Methods: We retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins. Univariate and multivariate analyses were performed to assess the prognostic significance of overexpressed genes.

Results: Median age was 56 years [35-78]. Most of patients were men (80%) with a history of alcohol (70.4%) and/or tobacco consumption (72.5%). Twelve patients (12%) were HPV-positive. Most significantly overexpressed genes involved cell cycle regulation (CCND1 [27%], CDK6 [21%]), tyrosine kinase receptors (MET [18%], EGFR [14%]), angiogenesis (PGF [301%], VEGFA [14%]), and immune system (PDL1/CD274 [28%]). PIK3CA expression was an independent prognostic marker, associated with shorter disease-free survival.

Conclusions: We identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients.

Keywords: clinical prognostic and theranognostic biomarkers; gene expression; head and neck squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • ErbB Receptors / genetics
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-met / genetics
  • RNA, Messenger / analysis
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • RNA, Messenger
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6