核酸酶（ENPP2）已被确定为肺癌和前列腺癌的潜在生物标志物，然而其在肝细胞癌（HCC）中的表达和临床相关性尚不完全了解。本研究使用生物信息学方法全面评估了ENPP2在多种癌症中的表达。我们使用TCGA数据库的数据，分析了ENPP2 mRNA在原发性肝癌及其相邻组织中的表达。使用Cox回归和Kaplan-Meier方法鉴定与生存相关的临床病理因素，并使用受试者工作特征曲线分析评估ENPP2表达的诊断价值。我们还通过对临床肝癌样本进行实时PCR验证了我们的发现。此外，我们还使用癌症基因组图谱数据集进行基因集富集分析，以了解ENPP2在HCC中的生物学意义。HCC患者ENPP2高表达与性别和临床分期有关，并且是预后较差的重要预后指标。ENPP2表达是两个队列中无进展生存和疾病特异性生存的独立危险因素，表明其作为HCC生物标志物的潜力。受试者工作特征曲线下的面积为0.806验证了ENPP2在HCC患者中的诊断价值。实时PCR分析验证了临床肝癌组织中ENPP2表达的增加。基因集富集分析确定了在ENPP2高表达的HCC患者中富集的通路，包括与细胞周期、MTOR和T细胞受体信号传导以及磷脂酰肌醇信号传导系统相关的通路。我们证明了ENPP2在HCC中高表达，并且是HCC诊断和预后的潜在独立分子标记物。版权所有 © 2023 作者。Wolters Kluwer Health, Inc.出版。

Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) has been identified as a potential biomarker in lung and prostate cancers; however, its expression and clinical relevance in hepatocellular carcinoma (HCC) remain incompletely understood. This study comprehensively assessed ENPP2 expression in pan-cancer using bioinformatics. We analyzed the expression of ENPP2 mRNA in primary liver cancer and adjacent tissues of patients with HCC using data from the TCGA database. Cox regression and Kaplan-Meier methods were used to identify clinicopathological factors associated with survival, and the diagnostic value of ENPP2 expression was evaluated using receiver operating characteristic curve analysis. We also validated our findings by performing real-time PCR on clinical liver cancer samples. Furthermore, we conducted gene set enrichment analysis using the Cancer Genome Atlas dataset to gain additional insights into the biological significance of ENPP2 in HCC. High ENPP2 expression in HCC patients is associated with gender and clinical stage, and is a significant prognostic factor for worse outcomes. ENPP2 expression is an independent risk factor for progression-free and disease-specific survival in both cohorts, suggesting its potential as an HCC biomarker. ENPP2's diagnostic value in HCC patients was confirmed by the area under the receiver operating characteristic curve, which was 0.806. real-time PCR analysis validated the higher expression of ENPP2 in clinical liver cancer tissues. Gene set enrichment analysis identified pathways enriched in HCC patients with high ENPP2 expression, including those related to the cell cycle, MTOR and T cell receptor signaling, and phosphatidylinositol signaling systems. We have demonstrated that ENPP2 is highly expressed in HCC and is a potential independent molecular marker for the diagnosis and prognosis of HCC.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.