A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

BMC Cancer. 2021 Sep 16;21(1):1035. doi: 10.1186/s12885-021-08765-w.

Abstract

Background: Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC.

Methods: Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model.

Results: TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies.

Conclusion: The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.

Keywords: Chemotherapy; Head and neck squamous cell carcinoma; Immunotherapy; Prognosis; TP53 mutation; Therapeutic response.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Databases, Genetic
  • Gene Expression
  • Genes, p53*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / mortality
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Kaplan-Meier Estimate
  • Mutation*
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Treatment Outcome
  • Tumor Microenvironment / immunology
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • TP53 protein, human
  • Tumor Suppressor Protein p53