Research Paper Volume 12, Issue 8 pp 7363—7379

Nudix hydrolase 1 is a prognostic biomarker in hepatocellular carcinoma

Qifeng Ou 1, *, , Ning Ma 2, *, , Zheng Yu 1, , Rongchang Wang 3, , Yucheng Hou 4, , Ziming Wang 5, , Fan Chen 7, , Wen Li 1, , Jiong Bi 1, , Jieyi Ma 1, , Longjuan Zhang 1, , Qiao Su 6, , Xiaohui Huang 1, ,

  • 1 Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 2 Department 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
  • 3 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China
  • 4 Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 5 Department of Pancreatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
  • 6 Animal Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 7 Department of Orthopaedic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
* Equal contribution

received: October 9, 2019 ; accepted: April 7, 2020 ; published: April 27, 2020 ;

https://doi.org/10.18632/aging.103083
How to Cite

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.

Abbreviations

AFP: alpha-fetoprotein; AJCC: American Joint Committee on Cancer; ANLT: adjacent normal liver tissue; AUC: area under the curve; CI: confidence interval; GEPIA: Gene Expression Profiling Interactive Analysis; GSEA: gene set enrichment analysis; GO: Gene Ontology; HCC: hepatocellular carcinoma; HR: hazard ratio; KEGG: Kyoto Encyclopedia of Genes and Genomes; MTH1: MutT Homolog1; NUDT1: Nudix hydrolase 1; OS: overall survival; PFS: progression-free survival; PID: Pathway Interaction Database; qRT-PCR: quantitative real-time polymerase chain reaction; RNA-seq: RNA sequencing; ROC: receiver operating characteristic curve; ROS: reactive oxygen species; TCGA: The Cancer Genome Atlas; TNM: tumour-node-metastasis; Tumor PT: tumor pathology.