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Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma

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Abstract

Background

PARP1-binding protein (PARPBP/PARI/C12orf48), a negative regulator of homologous recombination (HR), has been suggested to function as an oncogene in cervical, lung, and pancreatic cancer.

Objective

To investigate the expression profile of PARPBP and its role in hepatocellular carcinoma (HCC).

Methods

Using data from the Cancer Genome Atlas and Human Protein Atlas databases, PARPBP expression level and its clinical implication in HCC were identified by t test and Chi-square test. The prognostic value of PARPBP in HCC was evaluated by Kaplan–Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) was used to screen biological pathways correlated with PARPBP expression in HCC.

Results

PARPBP was significantly upregulated in HCC tissues compared with normal liver tissues (P < 0.05). High PARPBP expression was significantly associated with elevated serum AFP level, vascular invasion, poor tumor differentiation, and advanced TNM stage (all P < 0.05). Kaplan–Meier analyses suggested that upregulation of PARPBP was correlated with worse overall survival (OS) and recurrence-free survival (RFS) in HCC. Multivariate analyses further confirmed that PARPBP upregulation was an independent indicator of poor OS and RFS (all P < 0.05). The prognostic nomograms based on PARPBP mRNA expression and TNM stage were superior to those based on the TNM staging system alone (all P < 0.05). Besides, PARPBP DNA copy gain and miR-139-5p downregulation were associated with PARPBP upregulation in HCC. GSEA revealed that “cell cycle,” “HR,” “DNA replication,” and “p53 signaling” pathways were enriched in high PARPBP expression group.

Conclusion

PARPBP may be a promising prognostic biomarker and candidate therapeutic target in HCC.

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Authors and Affiliations

  1. Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People’s Republic of China

    Bin Yu, Youming Ding, Bin Wang & Xiaoyan Chen

  2. Department of General Surgery, Xiangyang Central Hospital, Xiangyang, 441021, Hubei Province, People’s Republic of China

    Xiaofeng Liao

  3. Department of Pathology and Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, Hubei Province, People’s Republic of China

    Changhua Wang

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  1. Bin Yu
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  2. Youming Ding
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  3. Xiaofeng Liao
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  4. Changhua Wang
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  5. Bin Wang
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  6. Xiaoyan Chen
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Correspondence to Youming Ding.

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Yu, B., Ding, Y., Liao, X. et al. Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma. Dig Dis Sci 64, 2878–2892 (2019). https://doi.org/10.1007/s10620-019-05608-4

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  • DOI: https://doi.org/10.1007/s10620-019-05608-4

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