Dataset Information

Overexpression of NR4A1 is associated with tumor recurrence and poor survival in non-small-cell lung carcinoma.

ABSTRACT: The expression level and clinical significance of NR4A1 are presently unknown in the non-small-cell lung carcinoma (NSCLC). This study aimed to explore the expression, prognostic value, and function of NR4A1 in NSCLC.Clinicopathological parameters of 167 NSCLC patients who received radical surgery from January 2007 and December 2012 were retrospectively reviewed. The NR4A1 expression in NSCLC tumors and the adjacent matched para-carcinoma specimens were examined, and the association between NR4A1 expression and clinical variables was explored. Cell viability assay, and transwell migration and invasion assays were used to access the function of NR4A1 in NSCLC. Kaplan-Meier analysis and Cox regression were performed to investigate the prognostic significance of NR4A1 for NSCLC.NR4A1 was overexpressed in NSCLC tissues compared with the para-carcinoma specimens. Consistently, Oncomine analysis showed that NR4A1 was overexpressed in NSCLC tissues compared with normal tissues in published datasets (P < 0.001). The elevated NR4A1 expression was associated with carcinoma recurrence (P < 0.05). The 5-year median overall survival (OS) and progression free survival (PFS) were significantly poorer in the NR4A1-overexpression group. Multivariate Cox analysis showed that NR4A1 overexpression was an independent factor for OS (HR, 95%CI: P < 0.05) and PFS (HR, 95%CI: P < 0.05) in NSCLC. Moreover, knockdown of NR4A1 significantly reduced NSCLC cell proliferation, migration, and invasion.NR4A1 exhibits a tumor-promoting effect on NSCLC, and might serve as a promising prognostic biomarker and a therapeutic target for NSCLC.

SUBMITTER: Zhu B

PROVIDER: S-EPMC5768379 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Overexpression of NR4A1 is associated with tumor recurrence and poor survival in non-small-cell lung carcinoma.

Zhu Bing B Yang Jian-Ru JR Jia Yang Y Zhang Pei P Shen Lin L Li Xiao-Long XL Li Jing J Wang Bing B

Oncotarget 20171208 69

The expression level and clinical significance of NR4A1 are presently unknown in the non-small-cell lung carcinoma (NSCLC). This study aimed to explore the expression, prognostic value, and function of NR4A1 in NSCLC.<h4>Methods</h4>Clinicopathological parameters of 167 NSCLC patients who received radical surgery from January 2007 and December 2012 were retrospectively reviewed. The NR4A1 expression in NSCLC tumors and the adjacent matched para-carcinoma specimens were examined, and the associat ...[more]

PMID: 29371962

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Project description:PurposeOur research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC).Materials and methodsGINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC.ResultsWGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway.ConclusionGINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.

Dataset Information

Overexpression of NR4A1 is associated with tumor recurrence and poor survival in non-small-cell lung carcinoma.

Publications

Overexpression of NR4A1 is associated with tumor recurrence and poor survival in non-small-cell lung carcinoma.

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