Abstract
APE1 is a multifunctional protein that plays important roles in cancer development. However, the association between APE1 expression and the clinicopathological parameters of HCC patients has not been fully characterized. In this study, bioinformatics analysis of APE1 was performed in several databases, including the TCGA, GeneCard, Human Protein Atlas and Ualcan databases. The relationship between APE1 mRNA expression and several attributes of liver cancer patients in TCGA was investigated. Then, the protein expression of APE1 was detected by IHC analysis in 95 HCC samples and the association between APE1 expression and the clinicopathological parameters of HCC patients was explored. GSEA-KEGG analysis was performed to predict the potential signaling pathways that associated with APE1 expression. Then the siRNA-mediated knockdown model of APE1 was constructed in HCC cell line to further detect the detailed function of APE1 in HCC development in vitro and in vivo. The results of the bioinformatics analysis showed that APE1 expression was primarily located in the cell nucleus. APE1 mRNA expression was substantially correlated with pathological grade and T status in TCGA database. Elevated APE1 expression was observed in HCC samples and was associated with unfavorable survival time in liver cancer patients. IHC data demonstrated that the nuclear expression of APE1 in HCC tissues was significantly higher than that in noncancerous tissues. The expression level of the APE1 protein in HCC was strongly associated with tumor diameter and overall survival. Survival analysis indicated that APE1 nuclear expression is an independent prognostic marker for the overall survival of HCC patients. GSEA-KEGG results confirmed that APE1 associated with the base excision repair signaling pathway. The data of phenotypic experiments indicated that APE1 remarkably promoted tumor growth both in HCC cells and xenografts. The findings firstly imply that nuclear expression of APE1 is a valuable prognostic marker for HCC. APE1 significantly facilitate HCC development and targeting APE1 may be a promising strategy for HCC treatment.
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This study is supported by the grant from the Nantong Basic Science Research Project (No. JC2018138).
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10735_2020_9939_MOESM1_ESM.png
Supplementary Figure S1. Protein interaction network construction. The predicted protein interactome of APE1 was extracted and analyzed in the STRING 10.5 database. This protein interaction network was constructed by Cytoscape 3.61. The protein encoded by APE1 is colored by red square, and the other neighboring proteins are shown by other colorful ellipses. Pearson's correlation analysis was performed in matched samples (linear regression analysis), and Pearson's correlation coefficients (R) are demonstrated in each plot. APE1 expression was positively correlated with the expression of PRMT5 (r = 0.72), TIMM9 (r = 0.72), DHX9 (r = 0.72), CHD8 (r = 0.73), SUPT16H (r = 0.82) and HNRNPC (r = 0.74). (PNG 181 kb)
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Lu, X., Zhao, H., Yuan, H. et al. High nuclear expression of APE1 correlates with unfavorable prognosis and promotes tumor growth in hepatocellular carcinoma. J Mol Histol 52, 219–231 (2021). https://doi.org/10.1007/s10735-020-09939-9
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DOI: https://doi.org/10.1007/s10735-020-09939-9