Yin Xin, Yu Hao, He Xing-Kang, Yan Sen-Xiang
Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China.
Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China.
World J Clin Cases. 2022 Mar 6;10(7):2072-2086. doi: 10.12998/wjcc.v10.i7.2072.
The N-Myc downstream-regulated gene (NDRG) family is comprised of four members (NDRG1-4) involved in various important biological processes. However, there is no systematic evaluation of the prognostic of the NDRG family in hepatocellular carcinoma (HCC).
To analyze comprehensively the biological role of the NDRG family in HCC.
The NDRG family expression was explored using The Cancer Genome Atlas. DNA methylation interactive visualization database was used for methylation analysis of the NDRG family. The NDRG family genomic alteration was assessed using the cBioPortal. Single-sample Gene Set Enrichment Analysis was used to determine the degree of immune cell infiltration in tumors.
NDRG1 and NDRG3 were up-regulated in HCC, while NDRG2 was down-regulated. Consistent with expression patterns, high expression of NDRG1 and NDRG3 was associated with poor survival outcomes ( < 0.05). High expression of NDRG2 was associated with favorable survival ( < 0.005). An NDRG-based signature that statistically stratified the prognosis of the patients was constructed. The percentage of genetic alterations in the NDRG family varied from 0.3% to 11.0%, and the NDRG1 mutation rate was the highest. NDRG 1-3 expression was associated with various types of infiltrated immune cells. Gene ontology analysis revealed that organic acid catabolism was the most important biological process related to the NDRG family. Gene Set Enrichment Analysis showed that metabolic, proliferation, and immune-related gene sets were enriched during NDRG1 and NDRG3 high expression and NDRG2 low expression.
Overexpression of NDRG1 and NDRG3 and down-expression of NDRG2 are correlated with poor overall HCC prognosis. Our results may provide new insights into the indispensable role of NDRG1, 2, and 3 in the development of HCC and guide a promising new strategy for treating HCC.
N-Myc下游调控基因（NDRG）家族由四个成员（NDRG1 - 4）组成，参与多种重要的生物学过程。然而，目前尚无对NDRG家族在肝细胞癌（HCC）中预后情况的系统评估。
全面分析NDRG家族在HCC中的生物学作用。
利用癌症基因组图谱（The Cancer Genome Atlas）探究NDRG家族的表达情况。使用DNA甲基化交互式可视化数据库对NDRG家族进行甲基化分析。通过cBioPortal评估NDRG家族的基因组改变。采用单样本基因集富集分析（Single-sample Gene Set Enrichment Analysis）确定肿瘤中免疫细胞浸润程度。
NDRG1和NDRG3在HCC中上调，而NDRG2下调。与表达模式一致，NDRG1和NDRG3的高表达与较差的生存结果相关（P<0.05）。NDRG2的高表达与良好的生存相关（P<0.005）。构建了一个基于NDRG的特征，可对患者的预后进行统计学分层。NDRG家族的基因改变百分比在0.3%至11.0%之间变化，其中NDRG1的突变率最高。NDRG 1 - 3的表达与多种类型的浸润免疫细胞相关。基因本体分析表明，有机酸分解代谢是与NDRG家族相关的最重要生物学过程。基因集富集分析显示，在NDRG1和NDRG3高表达以及NDRG2低表达期间，代谢、增殖和免疫相关基因集富集。
NDRG1和NDRG3的过表达以及NDRG2的低表达与HCC总体预后不良相关。我们的结果可能为NDRG1、2和3在HCC发生发展中的不可或缺作用提供新见解，并为治疗HCC指引一种有前景的新策略。
