Abstract
BACKGROUND: ENOPH1 (Enolase-phosphatase 1), a member of the HAD-like hydrolase superfamily, has been linked to a range of physiological conditions, including neurological disorders. However, its involvement in tumorigenesis remains underexplored. This study is the first to conduct a pan-cancer analysis of ENOPH1, aiming to elucidate its role in multiple cancers through various bioinformatics platforms. METHODS: We conducted a thorough analysis using data from UCSC databases. ENOPH1 expression in tumor and normal tissues was evaluated using R language software. Survival analyses, genetic alterations, and RNA modifications were assessed through the GEPIA2 and cBioPortal platforms. The relationships between ENOPH1 and immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) were examined using TIMER2 and R software. ENOPH1-related gene enrichment analysis was performed using the STRING and GEPIA2 databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. RESULTS: ENOPH1 expression was significantly upregulated in various cancers, including ACC, BLCA, BRCA, and COAD. High ENOPH1 expression was associated with poor overall survival (OS) in cancers such as KICH, LIHC, BRCA and LUAD. High ENOPH1 expression was associated with poor disease specific survival (DSS) in cancers such as KICH, LIHC, BRCA and MESO. Genetic alterations of ENOPH1, primarily mutations and deep deletions, were identified in UCEC, BLCA, and OV. ENOPH1 showed significant correlations with RNA modifications (m1A, m5C, m6A), immune checkpoints, and immune modulators across multiple cancer types. ENOPH1 was positively correlated with TMB, MSI, and HRD in cancers like BLCA, BRCA, and STAD. Furthermore, enrichment analysis revealed that ENOPH1 interacts with proteins involved in critical pathways such as AMPK, Hippo, and PI3K-AKT, suggesting its role in cancer progression. CONCLUSION: This pan-cancer analysis reveals ENOPH1's potential as a prognostic biomarker and its involvement in key signaling pathways across multiple cancers. Our findings provide new insights into the role of ENOPH1 in tumorigenesis and highlight its potential as a therapeutic target in cancer treatment.