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Research Paper|Volume 12, Issue 8|pp 7363—7379

Nudix hydrolase 1 is a prognostic biomarker in hepatocellular carcinoma

Qifeng Ou1, Ning Ma2, Zheng Yu1, Rongchang Wang3, Yucheng Hou4, Ziming Wang5, Fan Chen7, Wen Li1, Jiong Bi1, Jieyi Ma1, Longjuan Zhang1, Qiao Su6, Xiaohui Huang1
  • 1Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 2Department of Gastrointestinal Surgery and Hernia Center, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Supported by National Key Clinical Discipline, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China
  • 3Department of Gastrointestinal Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China
  • 4Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 5Department of Pancreatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
  • 6Animal Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 7Department of Orthopaedic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
* Equal contribution
Received: October 9, 2019Accepted: April 7, 2020Published: April 27, 2020
https://doi.org/10.18632/aging.103083

Copyright © 2020 Ou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.