Journal
AGING-US
Volume 13, Issue 1, Pages 351-363Publisher
IMPACT JOURNALS LLC
Keywords
breast cancer; tumor mutational burden; immune infiltration; ADRB1; prognosis
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Funding
- National Natural Science Foundation of China [81673799, 81703915, 81973677]
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Breast cancer (BRCA) has traditionally been considered to have poor immunogenicity and low tumor mutational burden (TMB). However, high TMB in BRCA is more likely to activate a partial immune response. The mutation of ADRB1, identified as a potential biomarker, is associated with lower TMB and shows a satisfactory clinical prognosis, providing new insights for co-therapy of BRCA.
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.
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