Yu Chaoran, Hao Xiaohui, Zhang Sen, Hu Wenjun, Li Jianwen, Sun Jing, Zheng Minhua
Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Department of Gastrointestinal Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Therap Adv Gastroenterol. 2019 Jul 21;12:1756284819858507. doi: 10.1177/1756284819858507. eCollection 2019.
The N-myc downstream-regulated gene () family, , has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the family in GC.
The prognostic values of the family were evaluated by Kaplan-Meier Plotter and SurvExpress. The mRNA of the family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the family was evaluated by the Tumor Immune Estimation Resource (TIMER) database.
High levels of mRNA expression of and were associated with a favorable prognosis in all GCs. In GC, was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16-2.33, = 0.0046]. In GC, showed a poor prognosis (HR = 1.4, 95% CI: 1.06-1.85, = 0.017). was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk -signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2-2.59, = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with and phosphorylated . Epidermis development was the top biological process (BP) for coexpressed genes associated with and , while mitotic nuclear division and mitotic cell processes were the top BPs for and , respectively. Overall, 6 CpGs of , 4 CpGs of , 3 CpGs of and 24 CpGs of were associated with significant prognosis. CD4 T-cells showed the highest correlation with (correlation = 0.341, = 2.14e). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with (correlation = 0.438, = 00e00).
This study analyzed the multilevel prognostic values and biological roles of the family in GC.
N-myc下游调控基因（NDRG）家族，即NDRG1、NDRG2、NDRG3和NDRG4，已参与多种癌症的广泛生物学功能。然而，它们在胃癌（GC）中的预后价值仍然有限。因此，系统研究NDRG家族在GC中的预后价值至关重要。
通过Kaplan-Meier Plotter和SurvExpress评估NDRG家族的预后价值。在癌症基因组图谱（TCGA）中研究NDRG家族的mRNA。通过NetworkAnalysis预测与NDRG家族相关的转录因子（TFs）和微小RNA（miRNAs）。通过MethSurv分析DNA甲基化水平的预后价值。通过肿瘤免疫估计资源（TIMER）数据库评估免疫细胞与NDRG家族之间的相关性。
NDRG1和NDRG4的高水平mRNA表达与所有GC患者的良好预后相关。在肠型GC中，NDRG2与GC的不良预后显著相关[风险比（HR）=1.65，95%置信区间（CI）=1.16-2.33，P=0.0046]。在弥漫型GC中，NDRG3显示出不良预后（HR=1.4，95%CI：1.06-1.85，P=0.017）。NDRG1是TCGA队列中无复发生存的独立预后因素。低风险NDRG特征组的生存结果明显优于高风险组（HR=1.76，95%CI：1.2-2.59，P=0.00385）。磷酸化蛋白NDRG1（NDRG1_pT346）显示出良好的总生存，并且与NDRG1和磷酸化NDRG2显著相关。表皮发育是与NDRG1和NDRG4共表达基因的首要生物学过程（BP），而有丝分裂核分裂和有丝分裂细胞过程分别是NDRG2和NDRG3的首要BP。总体而言，NDRG1的6个CpG、NDRG2的4个CpG、NDRG3的3个CpG和NDRG4的24个CpG与显著预后相关。CD4 T细胞与NDRG4的相关性最高（相关性=0.341，P=2.14e-05）。此外，滤泡辅助性T细胞（Tfh）中的BCL6与NDRG3的相关性最高（相关性=0.438，P=0.00e00）。
本研究分析了NDRG家族在GC中的多层次预后价值和生物学作用。
