Dataset Information

NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer.

ABSTRACT:

Background

Nuclear receptors (NRs) are a class of transcription factors that regulate many cellular functions through manipulation of gene expression and also play important roles in tumorigenesis, proliferation, progression and prognosis in various kinds of cancers according to recent studies. This work aimed to determine the predictive ability of NRs in muscle-invasive bladder cancer (MIBC).

Patients and methods

A total of 308 MIBC patients with complete clinicopathological and RNASeq data from The Cancer Genome Atlas (TCGA) cohort were collected for filtration. Genes showed clear correlations with overall survival (OS) and recurrence free survival (RFS) were further validated in 123 MIBC patients recruited consecutively from 2008 to 2012 in Fudan University Shanghai Cancer Center (FUSCC) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors.

Results

In TCGA cohort, we found that high NR1H3 (HR=0.779, 95% CI: 0.634 - 0.957), NR2C1 (HR=0.673, 95% CI: 0.458 - 0.989) and NR2F6 (HR=0.750, 95% CI: 0.574 - 0.980) expressions were independent factors of favorable OS, while only low NR1H3 (log-rank test, P=0.0076) and NR2F6 (log-rank test, P=0.0395) expressions had the ability to predict poor prognosis for RFS. Further, in FUSCC validating cohort, we confirmed that low NR1H3 expression level was independent factor of poor OS (HR=1.295, 95% CI: 1.064 - 1.576) and it had the ability to predict poor RFS (log-rank test, P=0.0059).

Conclusions

Low NR1H3 expression level is an independent prognostic factor of poor OS, and can also predict worse RFS in MIBC patients. Our "TCGA filtrating and local database validating" model can help reveal more prognostic biomarkers and cast a new light in understanding certain gene function in MIBC.

SUBMITTER: Wu J

PROVIDER: S-EPMC5381174 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer.

Wu Junlong J Wan Fangning F Sheng Haoyue H Shi Guohai G Shen Yijun Y Lin Guowen G Dai Bo B Zhu Yiping Y Ye Dingwei D

Journal of Cancer 20170307 5

<h4>Background</h4>Nuclear receptors (NRs) are a class of transcription factors that regulate many cellular functions through manipulation of gene expression and also play important roles in tumorigenesis, proliferation, progression and prognosis in various kinds of cancers according to recent studies. This work aimed to determine the predictive ability of NRs in muscle-invasive bladder cancer (MIBC).<h4>Patients and methods</h4>A total of 308 MIBC patients with complete clinicopathological and ...[more]

PMID: 28382148

Similar Datasets

Project description:BackgroundThe fatality and recurrence rates of bladder cancer (BC) have progressively increased. DNA methylation is an influential regulator associated with gene transcription in the pathogenesis of BC. We describe a comprehensive epigenetic study performed to analyse DNA methylation-driven genes in BC.MethodsData related to DNA methylation, the gene transcriptome and survival in BC were downloaded from The Cancer Genome Atlas (TCGA). MethylMix was used to detect BC-specific hyper-/hypo-methylated genes. Metascape was used to carry out gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A least absolute shrinkage and selection operator (LASSO)-penalized Cox regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related methylation-driven genes. Subsequently, we developed a six-gene risk evaluation model and a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic significance of the six genes.ResultsIn total, 167 methylation-driven genes were identified. Based on the LASSO Cox regression, six genes, i.e., ARHGDIB, LINC00526, IDH2, ARL14, GSTM2, and LURAP1, were selected for the development of a risk evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better OS (P?=?1.679e-05). The area under the curve (AUC) of this model was 0.698 at 3 years of OS. The verification performed in subgroups demonstrated the validity of the model. Then, we designed an OS-associated nomogram that included the risk score and clinical factors. The concordance index of the nomogram was 0.694. The methylation levels of IDH2 and ARL14 were appreciably related to the survival results. In addition, the methylation and gene expression-matched survival analysis revealed that ARHGDIB and ARL14 could be used as independent prognostic indicators. Among the six genes, 6 methylation sites in ARHGDIB, 3 in GSTM2, 1 in ARL14, 2 in LINC00526 and 2 in LURAP1 were meaningfully associated with BC prognosis. In addition, several abnormal methylated sites were identified as linked to gene expression.ConclusionWe discovered differential methylation in BC patients with better and worse survival and provided a risk evaluation model by merging six gene markers with clinical characteristics.

Project description:Bladder cancer (BLCA) is the most common urinary tract tumor and is the 11th most malignant cancer worldwide. With the development of in-depth multisystem sequencing, an increasing number of prognostic molecular markers have been identified. In this study, we focused on the role of protein-coding gene methylation in the prognosis of BLCA. We downloaded BLCA clinical and methylation data from The Cancer Genome Atlas (TCGA) database and used this information to identify differentially methylated genes and construct a survival model using lasso regression. We assessed 365 cases, with complete information regarding survival status, survival time longer than 30 days, age, gender, and tumor characteristics (grade, stage, T, M, N), in our study. We identified 353 differentially methylated genes, including 50 hypomethylated genes and 303 hypermethylated genes. After annotation, a total of 227 genes were differentially expressed. Of these, 165 were protein-coding genes. Three genes (zinc finger protein 382 (ZNF382), galanin receptor 1 (GALR1), and structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1)) were selected for the final risk model. Patients with higher-risk scores represent poorer survival than patients with lower-risk scores in the training set (HR = 2.37, 95% CI 1.43-3.94, p = 0.001), in the testing group (HR = 1.85, 95% CI 1.16-2.94, p = 0.01), and in the total cohort (HR = 2.06, 95% CI 1.46-2.90, p < 0.001). Further univariate and multivariate analyses using the Cox regression method were conducted in these three groups, respectively. All the results indicated that risk score was an independent risk factor for BLCA. Our study screened the different methylation protein-coding genes in the BLCA tissues and constructed a robust risk model for predicting the outcome of BLCA patients. Moreover, these three genes may function in the mechanism of development and progression of BLCA, which should be fully clarified in the future.

Dataset Information

NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer.

Background

Patients and methods

Results

Conclusions

Publications

NR1H3 Expression is a Prognostic Factor of Overall Survival for Patients with Muscle-Invasive Bladder Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets