170P - Clinical significance and functional role of GPR56 (ADGRG1) in breast cancer

Background

The clinical significance and functional role of adhesion G protein-coupled receptors (aGPCRs) in breast cancer remain largely unknown. We aimed to comprehensively analyze the prognostic potential of aGPCRs in breast cancer, identify the key prognostic GPCRs, and comprehend their functional roles.

Methods

A total of 1593 breast patients were analyzed using RNA-seq and clinical data from four independent public datasets, including 1064 patients from TCGA, 198 from GSE7390, 327 from GSE20685, and 104 from GSE42568. We also analyzed the mutated landscape based on exome and copy number alteration data from TCGA. In addition, single-cell RNA-seq (scRNA-seq) data from three breast cancer patients from GSE198745, and data on mammary gland tissue from the Tabula Muris, were used to measure the variation of the candidate GPCRs across diverse cell types. The CellMiner database was used to examine drug sensitivity.

Results

Among the 33 aGPCRs, GPR56 was the only significant prognostic factor in all four datasets. High GPR56 expression was significantly lined to worse relapse-free survival and overall survival. GPR56 expression was higher in younger, high-grade, and triple-negative breast cancers. GPR56-related genes were involved in several pathways, including cell division, DNA replication, cell cycle, protein binding, and others. GPR56 also participated in the activation of multiple cancer signaling pathways. High GPR56 expression was correlated with higher levels of several immune cells, immune checkpoints, and immune-related scores. scRNA-seq analysis revealed that GPR56 was mainly expressed in tumor cells, tumor stem cells and endothelial cells. In normal breast tissues, GPR56 expression was higher in basal cell subsets than in luminal epithelial cell subsets, suggesting that GPR56 may interact with breast stem cells. In addition, there were some differences in the mutant landscape between the high and low GPR56 expression groups. Furthermore, GPR56 was significantly associated with sensitivity to multiple antitumor drugs.

Conclusions

GPR56 was significantly linked to the molecular pathology and prognosis of breast cancer. GPR56 may serve as a promising novel therapeutic target in breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was supported by grants 82273204, 81972471 and 82073408 from the National Natural Science Foundation of China, grant 2023A1515012412 and 2023A1515011214 GuangDong Basic and Applied Basic Research Foundation, grant 2023A03J0722, 202206010078 and 202201020574 from the Guangzhou Science and Technology Project, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, grant A2020558 from the Guangdong Medical Science and Technology Program, grant 7670020025 from Tencent Charity Foundation , grant YXQH202209 from the Scientific Research Launch Project of Sun Yat-Sen Memorial Hospital, grant HL2021012 from the nursing research project of Sun Yat-Sen Memorial Hospital.

Disclosure

All authors have declared no conflicts of interest.