4.6 Article

Nudix hydrolase 1 is a prognostic biomarker in hepatocellular carcinoma

Journal

AGING-US
Volume 12, Issue 8, Pages 7363-7379

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.103083

Keywords

hepatocellular carcinoma; NUDT1; biomarker; survival analysis; nomogram

Funding

  1. National Natural Science Foundation of China [81472253, 81472258, 81572424, 81101862, 81172079, 81072047, 81201930]
  2. Natural Science Foundation of Guangdong Province [2014A030313063]
  3. Project of Guangzhou Municipal Science and Technology Planning [201607010309, 201607010164]
  4. Science and Technology Planning Project of Guangdong Province [2014A020212083, 2016A020215047, 2016A030303005, 2017A020215016]

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We investigated the prognostic significance of Nudix hydrolase 1 (NUDT1) in hepatocellular carcinoma (HCC). NUDT1 mRNA and protein levels were significantly higher in HCC tissues than normal liver tissues. The level of NUDT1 expression correlated with tumor grade, stage, size, differentiation, degree of vascular invasion, overall survival (OS), and disease-free survival (DFS) in HCC patients. Multivariate analysis showed that NUDT1 expression was an independent prognostic factor for OS and DFS in HCC patients. We constructed a prognostic nomogram with NUDT1 expression, AFP levels, vascular invasion, Child-Pugh classification, age, sex, AJCC staging, and tumor differentiation as variables. This nomogram was highly accurate in predicting the 5-year OS of HCC patients (c-index= 0.709; AUC= 0.740). NUDT1 silencing in HCC cells significantly reduced their survival, colony formation, migration, and invasiveness. Gene set enrichment analysis showed that biological pathways related to cell cycle, fatty acid metabolism, bile acid and bile salt metabolism, and PLK1 signaling were associated with NUDT1, as were the gene ontology terms DNA binding transcription activator activity, RNA polymerase II, nuclear division, and transmembrane transporter activity. Our study thus demonstrates that NUDT1 is a prognostic biomarker with therapeutic potential in HCC patients.

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