EPDR1 correlates with immune cell infiltration in hepatocellular carcinoma and can be used as a prognostic biomarker

Abstract

Background: Hepatocellular carcinoma (HCC) has high mortality rate and is a serious disease burden globally. Hence, identification and characterization of novel biomarkers for the diagnosis and prognosis of HCC are critically important. The protein EPDR1 (ependymin related 1) is a member of piscine brain glycoproteins and is involved in cell adhesion. This is the first study to report the expression of EPDR1 and its prognostic significance, pathological role, and association with cancer immunity in HCC.Methods: The gene expression, prognostic, and clinicopathological analyses were performed based on the data obtained from multiple transcriptome databases. Protein expression of EPDR1 in HCC was verified using human protein atlas and CPTAC databases. Co-expression network analysis using the LinkedOmics database was performed to identify genes co-expressed with EPDR1 expression. Functional analysis of the co-expressed genes, including gene set enrichment analysis was performed to identify the functional role of EPDR1. The statistical analysis was conducted in R, and the relationship between EPDR1 expression and immune cell infiltration was analyzed using TIMER and CIBERSORT resources. Results: The expression of EPDR1 was found to be significantly higher in HCC tissues than in the normal tissues and is an independent prognostic factor for the overall survival of HCC patients. Further, a high level of EPDR1 was shown to be correlated with advanced stage of HCC. Functional analysis revealed that EPDR1 is associated with multiple signaling pathways as well as pathways related to cancer and apoptosis. Notably, EPDR1 expression significantly correlated with purity and the infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Further, the EPDR1 expression significantly correlated with the expression of immune signatures, such as KIR2DL4, ITGAM, GATA3, STAT6, STAT5A, BCL6, STAT3, and HAVCR2.Conclusions: Our study identified EPDR1 as a novel prognostic biomarker in HCC. The expression of EPDR1 was shown to be associated with immune cell infiltration as well as the signature molecules that potentially regulate these processes during the carcinogenesis of HCC. With better understanding of its biological function, EPDR1 could become an effective target for HCC diagnosis and treatment in the future.