Ma Jiaxiu, Jin Jiapei, Lu Huishuang, Zhang Jin, Li Yalan, Cai Xuefei
The Key Laboratory of Molecular Biology of Infectious Diseases Designated By the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
Front Mol Biosci. 2022 Jun 13;9:889414. doi: 10.3389/fmolb.2022.889414. eCollection 2022.
Hepatocellular carcinoma (HCC) represents a global health challenge. Effective biomarkers are required for an early diagnosis to improve the survival rates of HCC patients. Exonuclease 1 (EXO1) plays a significant role in the DNA repair and recombination mechanisms. This study aimed to investigate the diagnostic and prognostic roles of EXO1 in HCC. We analyzed the EXO1 expression levels in various cancers including HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA sequencing data were analyzed using the R packages to determine differentially expressed genes (DEGs) between high- and low-EXO1 expressing HCC tissues from the TCGA-LIHC database. A Spearman's correlation analysis was performed to determine the association between EXO1 expression and immune cell infiltration, and immune checkpoint genes and TP53. MethSurv and CBioPortal databases were used to evaluate the DNA methylation changes and genetic alterations in the gene. A logistic regression analysis was performed to determine the association between EXO1 expression and the clinicopathological characteristics of the HCC patients. The diagnostic and prognostic predictive values of EXO1 were evaluated using the Kaplan-Meier (K-M) survival curves, diagnostic receiver operating characteristic (ROC) curves, nomogram model, and Cox regression analysis. EXO1 expression levels were significantly higher in the tumor tissues and serums of HCC patients compared to the corresponding controls. The DEGs associated with EXO1 were significantly enriched in the cell proliferation pathways. EXO1 expression levels significantly correlated with immune cell infiltration, immune checkpoint genes, and TP53 in the HCC tissues. The DNA methylation status in five CpG islands of the gene was associated with the prognosis of HCC. EXO1 expression levels in the HCC tissues were associated with the tumor grades, alpha-fetoprotein (AFP) levels, and the tumor stages. Cox regression analysis showed that EXO1 was a potential independent risk factor for the overall survival (OS) and disease-specific survival (DSS) of HCC patients. ROC curve analysis showed that EXO1 expression levels accurately distinguished HCC tissues from the adjacent normal liver tissues. Our study demonstrated that EXO1 was a potential diagnostic and prognostic biomarker, and a promising therapeutic target in HCC.
肝细胞癌（HCC）是一项全球性的健康挑战。早期诊断需要有效的生物标志物以提高HCC患者的生存率。核酸外切酶1（EXO1）在DNA修复和重组机制中发挥重要作用。本研究旨在探讨EXO1在HCC中的诊断和预后作用。我们分析了来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中包括HCC在内的各种癌症中的EXO1表达水平。使用R软件包分析RNA测序数据，以确定来自TCGA-LIHC数据库中高表达和低表达EXO1的HCC组织之间的差异表达基因（DEG）。进行Spearman相关性分析以确定EXO1表达与免疫细胞浸润、免疫检查点基因和TP53之间的关联。使用MethSurv和CBioPortal数据库评估该基因的DNA甲基化变化和基因改变。进行逻辑回归分析以确定EXO1表达与HCC患者临床病理特征之间的关联。使用Kaplan-Meier（K-M）生存曲线、诊断受试者工作特征（ROC）曲线、列线图模型和Cox回归分析评估EXO1的诊断和预后预测价值。与相应对照相比，HCC患者肿瘤组织和血清中的EXO1表达水平显著更高。与EXO1相关的DEG在细胞增殖途径中显著富集。HCC组织中EXO1表达水平与免疫细胞浸润、免疫检查点基因和TP53显著相关。该基因五个CpG岛中的DNA甲基化状态与HCC的预后相关。HCC组织中的EXO1表达水平与肿瘤分级、甲胎蛋白（AFP）水平和肿瘤分期相关。Cox回归分析表明，EXO1是HCC患者总生存（OS）和疾病特异性生存（DSS）的潜在独立危险因素。ROC曲线分析表明，EXO1表达水平能够准确区分HCC组织与相邻正常肝组织。我们的研究表明，EXO1是一种潜在的诊断和预后生物标志物，也是HCC中有前景的治疗靶点。
