EDNRA regulates the tumour immune environment and predicts the efficacy and prognosis of cancer immunotherapy

Abstract

The potential role of endothelin receptor A (EDNRA) in cancer immunotherapy has been demonstrated; however, the mechanism of its therapeutic value remains to be investigated. This study aimed to reveal the potential link between cancer immunotherapy and EDNRA in human tumours. Clinical characteristics and gene expression information were acquired from the Cancer Genome Atlas database. The correlation between EDNRA expression and immune infiltration was analysed by tumour immune estimation resource (TIMER) and tumour-immune system interaction database (TISIDB). EDNRA expression in different cancer types were performed via qPCR. Immunohistochemistry was used to detect the relationships between EDNRA protein and immune checkpoints. The results have founded that EDNRA was differentially expressed in various tumours, and highly associated with patient's age and tumour stage. It is also of high potential prognostic value in predicting patient survival. It has been verified that the EDNRA, JAK–STAT, and TGF-β signalling pathways are involved in cancers. In general, EDNRA positively correlated with immunomodulatory agents, immune cell infiltration, and immunotherapy markers. Immunohistochemical analysis of breast cancer tissues showed that EDNRA was positively correlated with NRP1 expression. Furthermore, patients with low EDNRA levels showed a superior response to immunotherapy. The functional study found that EDNRA expression is upregulated in MDA-MB-231 and HepG2 cells, and knockdown of EDNRA inhibits proliferation and migration of cells. In conclusion, the immunotherapeutic function of EDNRA was elucidated in this study. EDNRA may be an important target in tumour immunotherapy and provide new insights for tumour immunotherapy.