The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study

Oral Oncol. 2020 Nov:110:104943. doi: 10.1016/j.oraloncology.2020.104943. Epub 2020 Sep 9.

Abstract

Objective: Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC).

Methods: TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups.

Results: High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients.

Conclusions: HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration.

Keywords: Bead and neck squamous cell carcinoma (HNSCC); Prognosis; TCGA; Tumor microenvironment; Tumor mutation burden (TMB).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Biomarkers, Tumor
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / etiology*
  • Squamous Cell Carcinoma of Head and Neck / mortality*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor