在泛癌分析中探索ADRB1作为肿瘤抑制基因和预后生物标志物的潜在作用。

Exploring the potential role of ADRB1 as a tumor suppressor gene and prognostic biomarker in pan-cancer analysis.

作者信息

Xu Shenghan, Wang Xinlei, Wang Yani, Liu Min, Chen Hao

机构信息

School of Clinical Medicine, Shandong Second Medical University, Weifang, 261053, Shandong, China.

Department of Neurology, Sunshine Union Hospital, Weifang, 261041, Shandong, China.

出版信息

Discov Oncol. 2025 May 16;16(1):790. doi: 10.1007/s12672-025-02460-z.

DOI:10.1007/s12672-025-02460-z

PMID:40379922

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12084207/

Abstract

BACKGROUND

The β-adrenergic receptor (β-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-adrenergic receptor (β-AR), β-AR has higher affinity for norepinephrine. However, the current research is mostly limited to the role of β-AR in cancer development, and the effect and mechanism of β-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.

摘要

背景

β-肾上腺素能受体（β-AR）是一种重要的膜受体，属于G蛋白偶联受体，由ADRB1编码。交感神经释放的去甲肾上腺素激活β-肾上腺素能受体。与β-肾上腺素能受体（β-AR）相比，β-AR对去甲肾上腺素具有更高的亲和力。然而，目前的研究大多局限于β-AR在癌症发生发展中的作用，β-AR对癌症预后的影响及机制仍不清楚。

方法

我们分析了ADRB1在不同类型癌症及相应正常组织中的表达情况。分析了ADRB1表达与癌症病理分级、分期及生存率之间的相关性。我们探讨了ADRB1在各种癌症中的甲基化水平。利用cBioPortal网站确定癌症组织中ADRB1的突变特征。此外，还利用CancerSEA网站探索ADRB1表达与癌症不同功能状态之间的相关性。我们还分析了ADRB1表达与免疫检查点（ICP）基因、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、新抗原及癌症浸润免疫细胞之间的相关性。

结果

我们的结果表明，在大多数实体癌中ADRB1表达下调。ADRB1表达与癌症预后显著相关。发现ADRB1高表达是几种癌症患者的保护因素。在某些癌症中，ADRB1表达与临床病理分期相关。功能相关性分析表明ADRB1在调节癌细胞多种生物学行为中起关键作用。ADRB1表达与癌症中的TMB、MSI、新抗原及免疫细胞浸润相关。