Zhang Xuezhong, Li Ning, Chu Tingting, Zhao Haijun, Liu Tonggang
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Laboratory Medicine, Zibo Central Hospital, Zibo, Shandong, China.
Discov Oncol. 2025 Feb 15;16(1):190. doi: 10.1007/s12672-025-01965-x.
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.
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.
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.
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.
ENOPH1（烯醇化酶磷酸酶1）是HAD样水解酶超家族的成员，与一系列生理状况有关，包括神经疾病。然而，其在肿瘤发生中的作用仍未得到充分研究。本研究首次对ENOPH1进行泛癌分析，旨在通过各种生物信息学平台阐明其在多种癌症中的作用。
我们使用来自加州大学圣克鲁兹分校（UCSC）数据库的数据进行了全面分析。使用R语言软件评估肿瘤组织和正常组织中ENOPH1的表达。通过GEPIA2和cBioPortal平台评估生存分析、基因改变和RNA修饰。使用TIMER2和R软件研究ENOPH1与免疫浸润、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和同源重组缺陷（HRD）之间的关系。使用STRING和GEPIA2数据库进行ENOPH1相关基因富集分析，随后进行基因本体（GO）和KEGG通路富集分析。
ENOPH1在多种癌症中显著上调，包括肾上腺皮质癌（ACC）、膀胱癌（BLCA）、乳腺癌（BRCA）和结肠癌（COAD）。在肾嫌色细胞癌（KICH）、肝细胞癌（LIHC）、乳腺癌和肺腺癌（LUAD）等癌症中，ENOPH1高表达与总体生存期（OS）较差相关。在KICH、LIHC、乳腺癌和间皮瘤（MESO）等癌症中，ENOPH1高表达与疾病特异性生存期（DSS）较差相关。在子宫内膜癌（UCEC）、膀胱癌和卵巢癌（OV）中发现了ENOPH1的基因改变，主要是突变和深度缺失。在多种癌症类型中，ENOPH1与RNA修饰（m1A、m5C、m6A）、免疫检查点和免疫调节剂显示出显著相关性。在膀胱癌、乳腺癌和胃癌（STAD）等癌症中，ENOPH1与TMB、MSI和HRD呈正相关。此外，富集分析表明，ENOPH1与参与关键通路（如AMPK、Hippo和PI3K-AKT）的蛋白质相互作用，提示其在癌症进展中的作用。
这项泛癌分析揭示了ENOPH1作为预后生物标志物的潜力及其在多种癌症关键信号通路中的参与。我们的研究结果为ENOPH1在肿瘤发生中的作用提供了新的见解，并突出了其作为癌症治疗中治疗靶点的潜力。
