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Characterization of the prognostic values of the NDRG family in gastric cancer.

ABSTRACT: Background:The N-myc downstream-regulated gene (NDRG) family, NDRG1-4, 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 NDRG family in GC. Methods:The prognostic values of the NDRG family were evaluated by Kaplan-Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results:High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2 - GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR)?=?1.65, 95% confidence interval (CI)?=?1.16-2.33, p?=?0.0046]. In HER2 + GC, NDRG4 showed a poor prognosis (HR?=?1.4, 95% CI: 1.06-1.85, p?=?0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR?=?1.76, 95% CI: 1.2-2.59, p?=?0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4+ T-cells showed the highest correlation with NDRG4 (correlation?=?0.341, p?=?2.14e-11). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation?=?0.438, p?=?00e+00). Conclusions:This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.

SUBMITTER: Yu C

PROVIDER: S-EPMC6647212 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Characterization of the prognostic values of the <i>NDRG</i> family in gastric cancer.

Yu Chaoran C Hao Xiaohui X Zhang Sen S Hu Wenjun W Li Jianwen J Sun Jing J Zheng Minhua M

Therapeutic advances in gastroenterology 20190721

<h4>Background</h4>The N-myc downstream-regulated gene (<i>NDRG</i>) family, <i>NDRG1-4</i>, 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 <i>NDRG</i> family in GC.<h4>Methods</h4>The prognostic values of the <i>NDRG</i> family were evaluated by Kaplan-Meier Plotter and SurvExpress. The mRNA of the <i>NDRG</ ...[more]

PMID: 31384305

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Project description:BackgroundCXCL family is a class of secreted growth factors signaling through G-protein-coupled receptors, and abnormal expression is associated with the growth and progression of many tumors. However, their prognostic value has been poorly studied in Epstein-Barr virus- (EBV-) associated gastric cancer (EBVaGC). Therefore, it is of great significance to explore the prognostic value of the CXCL family in EBVaGC.MethodsCXCL family mRNA expression was analyzed in STAD data from The Cancer Genome Atlas (TCGA). Kaplan-Meier Plotter was used to assess the prognostic value of the CXCL family. Transcription factors (TFs) and miRNAs associated with the CXCL family were identified by TFCheckpoint, miRWalk, and ViRBase databases. The prognostic model was evaluated using the EBVaGC patient cohort GSE51575.ResultsThe mRNA expression of CXCL1/3/5/6/8/9/10/11/16 was significantly upregulated, while the expression of CXCL12/14 was downregulated in EBVaGC compared with normal tissues from TCGA-STAD. The mRNA expressions of CXCL9, CXCL10, CXCL11, and CXCL17 in EBVaGCs were higher than those in EBVnGCs, but the mRNA expressions of CXCL6, CXCL12, and CXCL17 were lower than those in EBVnGCs. The mRNA expression levels of CXCL9, CXCL10, and CXCL11 in EBVaGCs were higher than those in EBVnGCs regardless of the tumor stage. High mRNA expression of CXCL8 was associated with better OS in patients with EBVaGC, while high expression of CXCL9 was associated with better OS in patients with EBVnGC. We obtained 10 candidate potential transcription factors (TFs) associated with CXCLs: OTOP3, NKX6-2, NKX2-2, FEV, SMYD1, TRIMSO, TBX10, CDX1, SLC26A3, and ARC. 576 miRNA-mRNA interactions were obtained. Among them, 65 miRNAs were predicted to be correlated with CXCL6, CXCL9, CXCL10, and CXCL11. Similar to the results of TCGA-STAD, the GSE51575 dataset also showed that the mRNA expression levels of CXCL1/3/9/10/11/16 were markedly enhanced in EBVaGC tissues compared with corresponding normal gastric mucosa tissues, while the mRNA expression levels of CXCL12/14 were significantly reduced. The mRNA expression levels of CXCL3/9/10/11/13/17 were increased in EBVaGC compared with EBVnGC tissues.ConclusionsThe expression differences of CXCL family members are closely associated with the progression of EBVaGC. Expression of CXCL9/10/11/17 mRNA may be a promising prognostic indicator for EBVaGC patients.

Dataset Information

Characterization of the prognostic values of the NDRG family in gastric cancer.

Publications

Characterization of the prognostic values of the <i>NDRG</i> family in gastric cancer.

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