Identification of therapeutic targets and prognostic biomarkers of the ephrin receptor subfamily in pancreatic adenocarcinoma

Abstract

Objectives We aimed to examine the significance of ephrin receptor A2 (EphA2) expression in pancreatic adenocarcinoma (PAAD) and its associated mechanism. Methods EphA2 mRNA expression patterns were compared in pancreatic cancer and normal tissues using GEPIA. Kaplan–Meier analysis was used to examine the correlation between EphA2 expression and PAAD patient prognosis. EphA2 gene methylation and associations with tumor immune cell infiltration were analyzed with UALCAN and TIMER, respectively. EphA2-interacting proteins were investigated with GeneMANIA, while STRING helped predict potentially relevant signaling pathways. EphA2 protein expression was examined with immunohistochemistry (IHC) in PAAD patient tissues. Results EphA2 was highly expressed in pancreatic cancer tissues and associated with pathological stage. PAAD patients with high EphA2 expression had shorter overall survival and disease-free survival times. EphA2 expression levels were significantly and positively associated with CD4+ T cell infiltration. EphA2 can interact with ENFNA1, ACP1, and CDC42. High EphA2 mRNA expression was enriched for regulation of cell size and cell proliferation. IHC assays suggested that pancreatic cancer tissues had higher EphA2 protein levels than normal pancreatic tissues. Conclusions EphA2 is highly expressed in PAAD and closely related to poor patient prognosis, and is therefore a potential biomarker and target for PAAD diagnosis and treatment.