Comprehensive analysis of multiple parameters associated with tumor immune microenvironment in ARID1A mutant cancers

Future Oncol. 2020 Oct;16(29):2295-2306. doi: 10.2217/fon-2020-0243. Epub 2020 Jul 8.

Abstract

Aim: To verify the relationship between ARID1A and tumor immune microenvironment thus immune checkpoint inhibitors (ICIs) response. Material & methods: Several public databases were used to characterize the association between ARID1A gene alteration and tumor immunity. Results: The gene mutation frequency was 8.2% in all cancer types. The ARID1A-mutated cancers have higher scores of mutation count, tumor mutational burden, neoantigen load (p < 0.001) and T cell repertoire, B cell repertoire diversity (p < 0.05). The gene mutation has tight association with multiple-activated immune cells. Survival analysis suggested that patients with ARID1A mutant cancers benefit more from ICIs treatment (p = 0.013). Conclusion: The ARID1A gene mutation was correlated with higher tumor immunogenicity and activated antitumor immune microenvironment, resulting in superior cohort that respond well to ICIs.

Keywords: ARID1A; immune checkpoint inhibitors; pan-cancers; tumor immune microenvironment; tumor immunogenicity.

MeSH terms

  • Alleles
  • Biomarkers, Tumor*
  • DNA-Binding Proteins / genetics*
  • Databases, Genetic
  • Disease Management
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasms / etiology*
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Prognosis
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Transcription Factors / genetics*
  • Tumor Microenvironment / genetics*
  • Tumor Microenvironment / immunology*

Substances

  • ARID1A protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Transcription Factors