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APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma.

ABSTRACT: 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.

SUBMITTER: Cao L

PROVIDER: S-EPMC7093175 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma.

Cao Lei L Cheng Hongwei H Jiang Qiuxia Q Li Hui H Wu Zhixian Z

Aging 20200313 5

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 t ...[more]

PMID: 32167932

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Project description:Background: 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. Methods: 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 EXO1 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. Results: 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 EXO1 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. Conclusion: Our study demonstrated that EXO1 was a potential diagnostic and prognostic biomarker, and a promising therapeutic target in HCC.

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Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown.MethodsTCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro.ResultsMRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro.ConclusionsWe demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

Dataset Information

APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma.

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APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma.

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