Dataset Information

Distinct expression and prognostic values of the replication protein A family in gastric cancer.

ABSTRACT: The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Meier analysis was used to compare the overall survival (OS) times of GC patients that expressed different levels of RPA proteins. RPA1, 2, and 3 expression levels were all significantly upregulated in gastric intestinal-type, diffuse gastric, and gastric mixed adenocarcinomas, compared with those in normal mucosal tissues. Moreover, high mRNA expression levels of RPA3 and 4 predicted poorer OS times in all GCs, as well as patients with human epidermal growth factor receptor 2-negative and -positive GC. The high-risk group, separated by RPA signature, showed a poorer outcome than the low-risk group. RPA3 was the most strongly correlated with CD4+ T-cell levels. In conclusion, RPAs are novel prognostic indicators in GC, and can also predict the features of immunological diseases. Future experimental investigation into the roles of RPAs concerning the pathogenesis and development of GC may provide a novel biomarker or therapeutic target, improving the prognosis of patients with GC.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7038973 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Distinct expression and prognostic values of the replication protein A family in gastric cancer.

Zhang Yujie Y Yu Chaoran C

Oncology letters 20200107 3

The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Me ...[more]

PMID: 32194677

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Project description:BackgroundThe 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.MethodsThe 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.ResultsHigh 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).ConclusionsThis study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.

Dataset Information

Distinct expression and prognostic values of the replication protein A family in gastric cancer.

Publications

Distinct expression and prognostic values of the replication protein A family in gastric cancer.

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