Abstract
BACKGROUND: G protein-coupled receptors (GPCRs) are widely involved in cell signal transduction, and their abnormal activation has been proved to be closely related to the occurrence and development of various cancers. However, the functions of a large number of members in the GPCR family have not been clarified. Among them, the orphan receptor GPR137B is particularly rare, and its role in tumors has been rarely studied systematically. METHODS: The expression of GPR137B in ESCC was confirmed using multi-database analysis and clinical tissue samples, and its prognostic value in ESCC was investigated. The role of GPR137B in ESCC was confirmed through in vivo and in vitro investigations. The probable mechanism of GPR137B in ESCC was investigated by GO and KEGG enrichment analysis and Western blotting. Bioinformatics analysis was employed to investigate the association of immune infiltration, while flow cytometry was utilised to validate the expression of PD-L1. Drug sensitivity analysis investigated the potential of GPR137B as a predictor of drug responsiveness. RESULTS: GPR137B had elevated levels in ESCC and was associated with unfavourable prognosis. GPR137B may enhance the proliferation, invasion, migration, and tumorigenesis of ESCC cells. GPR137B was associated with the non-classical Wnt/PCP signalling pathway in enrichment analyses. The suppression of GPR137B facilitated the epithelial-mesenchymal transition (EMT) by reducing the expression of Wnt5A, FZD6, and p-JNK, proteins associated with the non-classical Wnt/PCP signalling pathway. The expression of GPR137B was correlated with immune infiltration in ESCC, and flow cytometry indicated a relationship with PD-L1. GPR137B may serve as a prognostic and therapeutic target for ESCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-026-04229-y.