Abstract
BACKGROUND: The β(1)-adrenergic receptor (β(1)-AR) is an important membrane receptor belonging to the G protein coupled receptors, encoded by ADRB1. Norepinephrine released by the sympathetic nerve activates β-adrenergic receptors. Compared with β(2)-adrenergic receptor (β(2)-AR), β(1)-AR has higher affinity for norepinephrine. However, the current research is mostly limited to the role of β(2)-AR in cancer development, and the effect and mechanism of β(1)-AR on cancer prognosis are still unclear. METHODS: We analyzed ADRB1 expression in different types of cancer and corresponding normal tissues. The correlation between ADRB1 expression and pathological grade, stage and survival of cancers were analyzed. We explored the methylation level of ADRB1 in various cancers. The cBioPortal website was used to determine the mutation characteristics of ADRB1 in cancer tissues. Additionally, the CancerSEA website was employed to explore the correlation between ADRB1 expression and different functional states in cancers. We also analyzed the correlation between ADRB1 expression and immune checkpoint (ICP) genes, tumor mutation burden (TMB), microsatellite instability (MSI), neoantigens and cancer-infiltrating immune cells. RESULTS: Our results showed that ADRB1 expression was downregulated in the majority of solid cancers. The ADRB1 expression was significantly associated with the prognosis of cancer. High expression of ADRB1 was found to be a protective factor for patients with several types of cancer. In some cancers, ADRB1 expression was associated with clinical pathological stages. Functional relevance analysis indicated the crucial role of ADRB1 in regulating multiple biological behaviors of cancer cells. The expression of ADRB1 was associated with TMB, MSI, neoantigens and immune cell infiltration in cancers. CONCLUSIONS: These comprehensive pan-cancer analysis suggested that ADRB1 plays a protective role in various cancer types, such as skin cutaneous melanoma and lung adenocarcinoma. This may provide a new idea for the clinical treatment of cancer patients.