By Carolina Brooks

Faculty Mentor: Dr. Sipe

Abstract

EPHB6 (ephrin type-b receptor 6) is a member of the receptor tyrosine kinase family that functions as a membrane receptor for ephrin-b ligands but lacks intrinsic kinase activity. It is frequently involved in carcinogenesis, metastasis, and regulation of cell adhesion and migration. Notably, EPHB6 is downregulated during tumor progression, suggesting a potential tumor-suppressive function.
This study investigated the relationship between EPHB6 expression, prognosis, metastasis, and potential response to anti-PD-L1 therapy in breast cancer. Data from Gene Set Cancer Analysis, Kaplan-Meier Plotter and TMNplot were analyzed across various subtypes, including basal, luminal A, luminal B and HER2. No statistically significant association was observed between expression and overall survival across subtypes. However, a non-significant trend toward worse survival was noted in HER2 subtype (p-value 0.08, HR 1.41). EPHB6 expression declined with advancing tumor stage, reaching its lowest levels at stage IV, suggesting an association with tumor progression and metastasis.
Additionally, EPHB6 expression showed a weak but statistically significant positive correlation with PD-L1 expression (Spearman r = 0.27, p < 0.01), suggesting a modest association with immune checkpoint activity. Evidence from bladder cancer studies further indicates that EPHB6 may predict immunotherapy response. Lower expression has been associated with increased sensitivity to anti-PD-L1 therapy, enhancing anti-tumor immunity by blocking inhibitory signals between T cells and tumor cells, whereas high expressions may be linked to resistance.
Overall, EPHB6 downregulation may serve as a biomarker of tumor progression and a potential predictor of response to anti-PD-L1 immunotherapy, highlighting the need for further research.