Integrative analysis of gene alterations and immunoexpression profiles of cell cycle checkpoints in oral squamous cell carcinoma

Cancer Biomark. 2020;27(1):95-103. doi: 10.3233/CBM-190776.

Abstract

Background: Oral squamous cell carcinoma (OSCC) represents 95% of all cancers of the head and neck region. The five-year survival rate of OSCC patients is about 60% and has not gone throw significant improvements despite recent advances in molecular biology, or the identification of key pathways in its pathophysiology such as cell cycle.

Objective: 1) to analyse the inmunoexpression of cell cycle checkpoints (CPs) in an OSCC institutional cohort and to relate it to clinicopathological features and survival, and 2) to study CPs-related genes in the OSCC subset of the TCGA database.

Methods: Immunohistochemistry (IHC) for p16INK4a, p21CIP1, cyclin D1 and p27KIP1 protein expression was quantified by tissue microarray analysis in 68 samples from OSCC patients. In order to analyse its correlation with genetic information, a cohort belonging to The Cancer Genome Atlas (TCGA) database was analysed.

Results: Of 68 patients, 34 (50%) developed recurrence, and 36 (52.09%) died as a result of disease progression (mean survival 34.09 months). IHC staining for nuclear cyclin D1 was associated with worse staging and tobacco use. p16INK4a, p21CIP1, cyclin D1, and p27KIP1 expression was unrelated to overall survival. No statistically significant correlation linked the CPs-related genes mutations to OSCC overall survival in the TCGA database.

Conclusions: CPs variations at a phenotype and genotype level seem not to affect significantly clinicopathological features and survival in the studied OSCC cohorts.

Keywords: Oral squamous cell carcinoma; cell cycle; cellular pathways/molecular mechanisms; expression profiling; molecular diagnosis.

MeSH terms

  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Checkpoints / genetics
  • Cyclin D1 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mouth Neoplasms / epidemiology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Progression-Free Survival
  • Tissue Array Analysis

Substances

  • CDKN1B protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27