Research Paper Volume 13, Issue 1 pp 351—363

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

Jia Wang1, , Xiaolu Zhang2, , Jie Li1, , Xiaoran Ma2, , Fubin Feng3, , Lijuan Liu3, , Jibiao Wu1, , Changgang Sun3,4, ,

  • 1 College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, P. R. China
  • 2 College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, P. R. China
  • 3 Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261000, Shandong, P. R. China
  • 4 Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China

Received: August 6, 2020       Accepted: September 29, 2020       Published: November 21, 2020
How to Cite

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


ADRB1: β-1 adrenergic receptor; BRCA: breast cancer; TMB: tumor mutational burden; TNBC: triple negative breast cancer; ICI: immune checkpoint inhibitor; TCGA: The Cancer Genome Atlas; Mb: megabase; DEG: differentially expressed gene; GSEA: Gene Set Enrichment Analysis; CNV: copy number variations; VEGFR1: vascular endothelial growth factor A; HIF1A: hypoxia inducible factor A; AR: adrenergic receptor; FDR: false discovery rate.