Role of the APEX family in hepatocellular carcinoma and its potential as a biomarker

Abstract

Objective To analyze the role of APEX family in hepatocellular carcinoma (HCC). Methods After expression data of HCC and normal liver tissues from public databases (TCGA and TNM plot) were collected, the expression patterns, functional networks, and potential biological pathways of the APEX family in HCC were investigated through differential expression analysis, construction of protein-protein interaction networks(PPI), and Gene Set Enrichment Analysis (GSEA). Receiver operating characteristic (ROC) curve analysis was used to assess the potential of APEX family members as diagnostic markers for HCC, and their correlation with HCC prognosis was anlyzed through survival analysis. RT-qPCR and Western blotting we performed to detect the expression of APEX1 and APEX2 at mRNA and protein levels in liver cells and HCC cells. The effect of silencing APEX1 and APEX2 in HCC cells were determined through CCK-8 assay, EdU assay, scratch healing test, and Transwell assay. Results The expression levels of the 2 members of the APEX family, APEX1 and APEX2, were significantly higher in the HCC samples than the normal liver tissues (P < 0.01). The results of ROC curve analysis on public databases showed that the AUC value of APEX1 and APEX2 in predicting HCC was 0.922 and 0.917, respectively. PPI network analysis revealed that APEX family members regulated cell cycle through various signaling pathways. Survival analysis indicated that HCC patients with high expression levels of APEX1 and APEX2 had significantly shorter overall survival than those with low levels (P < 0.05), and APEX1 and APEX2 were highly correlated with traditional tumor survival prognostic factors Ki-67 and TP53 (P < 0.001). The mRNA and protein levels of APEX1 and APEX2 were significantly higher in the liver cancer cells than the normal liver cells (P < 0.05). In addition, silencing APEX1 and APEX2 resulted in notably reduced proliferation, migration, and invasion abilities of HCC cells (P < 0.05). Conclusion APEX1 and APEX2 can serve as potential biomarkers for HCC diagnosis and prognosis assessment, and their involvement in the regulation of HCC proliferation and metastasis provides new strategies and targets for the early diagnosis and individualized treatment of HCC.

Keywords

• hepatocellular carcinoma
• apex family
• diagnostic biomarkers
• therapeutic targets
• bioinformatics analysis