Department of Hepatobiliary Disease, Dongfang Hospital, Xiamen University, Fuzhou, China.
The 900th Hospital of the People's Liberation Army Joint Service Support Force, Fuzhou, China.
Aging (Albany NY). 2020 Mar 13;12(5):4573-4591. doi: 10.18632/aging.102913.
In this study, we analyzed the expression and clinical significance of apyrimidinic endodeoxyribonuclease 1 (APEX1) in hepatocellular carcinoma (HCC). The APEX1 mRNA and protein levels were significantly higher in HCC than adjacent normal liver tissues in multiple datasets from the Oncomine, GEO and TCGA databases. APEX1 levels were significantly higher in early-stage HCC patients with low alpha-fetoprotein expression. The positive predictive value (PPV) for APEX1 was significantly higher than the PPV for alpha-fetoprotein (67.91% vs. 55.22%) in HCC patients. High APEX1 expression correlated with resistance to sorafenib and anti-programmed death 1 (PD-1) therapies in HCC patients, and it associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in early- and advanced-stage HCC patients. High APEX1 expression also associated with poor prognosis in non-alcoholic, vascular invasion-negative, and hepatitis virus-negative HCC patients. These data suggest that APEX1 is a better diagnostic and prognostic biomarker than alpha-fetoprotein in HCC. Gene set enrichment analysis (GSEA) showed that APEX1 expression correlated with the DNA damage repair pathway in HCC tissues. These findings demonstrate that APEX1 is a potential diagnostic and prognostic biomarker in HCC.
在这项研究中，我们分析了天冬氨酸肽酶 1（APEX1）在肝细胞癌（HCC）中的表达及其临床意义。来自 Oncomine、GEO 和 TCGA 数据库的多个数据集显示，APEX1mRNA 和蛋白水平在 HCC 中明显高于相邻的正常肝组织。在甲胎蛋白（AFP）低表达的早期 HCC 患者中，APEX1 水平明显升高。在 HCC 患者中，APEX1 的阳性预测值（PPV）明显高于 AFP（67.91%比 55.22%）。在 HCC 患者中，高 APEX1 表达与对索拉非尼和抗程序性死亡受体 1（PD-1）治疗的耐药性相关，并且与早期和晚期 HCC 患者的总生存期、疾病特异性生存期、无进展生存期和无复发生存期较差相关。高 APEX1 表达也与非酒精性、无血管侵犯和无肝炎病毒的 HCC 患者的不良预后相关。这些数据表明，APEX1 是比 AFP 更好的 HCC 诊断和预后生物标志物。基因集富集分析（GSEA）显示，APEX1 表达与 HCC 组织中的 DNA 损伤修复途径相关。这些发现表明 APEX1 是 HCC 潜在的诊断和预后生物标志物。
