ADRB1 was identified as a potential biomarker for breast cancer by the co-analysis of tumor mutational burden and immune infiltration

Aging (Albany NY). 2020 Nov 21;13(1):351-363. doi: 10.18632/aging.104204. Epub 2020 Nov 21.

Abstract

Breast cancer (BRCA) has traditionally been considered as having poor immunogenicity and is characterized by relatively low tumor mutational burden (TMB). Improving immunogenicity may improve the response to clinical immunotherapy of BRCA. However, the relationship between TMB, immune infiltration, and prognosis in BRCA remains unclear. We aimed to explore their interrelations and potential biomarkers. In this study, based on somatic mutation data of BRCA from The Cancer Genome Atlas (TCGA), patients were categorized into high and low TMB groups utilizing the TMB values. CIBERSOFT algorithm indicated significant infiltration of activated partial immune cells in high TMB group. Besides, ADRB1 had been identified as a prognosis-related immune gene in the mutant genes by the combination of the ImmPort database and the univariate Cox analysis. ADRB1 mutation was associated with lower TMB and manifested a satisfactory clinical prognosis. Various database applications (Gene Set Enrichment Analysis, Tumor IMmune Estimation Resource, Connectivity Map, KnockTF) supported the selection of treatment strategies targeting ADRB1. In conclusion, TMB was not an independent prognostic factor for BRCA and high TMB was more likely to activate a partial immune response. ADRB1 was identified as a potential biomarker and may provide new insights for co-therapy of BRCA.

Keywords: ADRB1; breast cancer; immune infiltration; prognosis; tumor mutational burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Databases, Genetic
  • Female
  • Humans
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mutation
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Adrenergic, beta-1 / genetics*

Substances

  • ADRB1 protein, human
  • Biomarkers, Tumor
  • Receptors, Adrenergic, beta-1