AUTHOR=Xu Shaohua , Gao Ruihuan , Zhou Yidan , Yang Ying , Zhang Yi , Li Qianyuan , Luo Chunhua , Liu Song-Mei 

TITLE=Clinical Diagnostic and Prognostic Potential of NDRG1 and NDRG2 in Hepatocellular Carcinoma Patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.862216

DOI=10.3389/fonc.2022.862216

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Primary liver cancer is still the most common lethal malignancy. The N-myc downstream-regulated gene family (<italic>NDRG1–4</italic>) is a group of multifunctional proteins associated with carcinogenesis. However, systematic evaluation of the diagnostic and prognostic values of <italic>NDRG1</italic> or <italic>NDRG2</italic> expression in liver cancer is poorly investigated.</p></sec><sec><title>Method</title><p>The gene expression matrix of liver hepatocellular carcinoma (LIHC) was comprehensively analyzed by the “limma” and “Dseq2” R packages. The Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the biological functional differences. A single-sample GSEA (ssGSEA) was conducted to quantify the extent of immune cell infiltration. Finally, the clinical and prognostic information of LIHC patients was systematically investigated using Kaplan–Meier analysis and logistic and Cox regression analysis.</p></sec><sec><title>Results</title><p>Compared with normal tissues, <italic>NDRG1</italic> expression was higher, whereas <italic>NDRG2</italic> expression was lower in tumor tissues (<italic>P &lt;</italic>0.001). The area under the receiver operator characteristic curve (AUROC) of <italic>NDRG1</italic> and <italic>NDRG2</italic> for LIHC was 0.715 and 0.799, respectively. Kaplan–Meier analysis revealed that <italic>NDRG1</italic> and <italic>NDRG2</italic> were independent clinical prognostic biomarkers for the overall survival (OS, <italic>P</italic> = 0.001 and 2.9e−06), progression-free interval (PFI, <italic>P</italic> = 0.028 and 0.005) and disease-specific survival (DSS, <italic>P</italic> = 0.027 and <italic>P &lt;</italic>0.001). The C-indexes and calibration plots of the nomogram suggest that <italic>NDRG1</italic> and <italic>NDRG2</italic> have an effective predictive performance for OS (C-index: 0.676), DSS (C-index: 0.741) and PFI (C-index: 0.630) of liver cancer patients. The mutation rate of <italic>NDRG1</italic> in liver cancer reached up to 14%, and DNA methylation levels of <italic>NDRG1</italic> and <italic>NDRG2</italic> promoters correlated significantly with clinical prognosis.</p></sec><sec><title>Conclusions</title><p>The mRNA expression and DNA methylation of <italic>NDRG</italic> superfamily members have the potential for LIHC diagnosis and prognosis <italic>via</italic> integrative analysis from multiple cohorts.</p></sec>