Dataset Information

Identification of a five-mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor.

ABSTRACT:

Background

The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT).

Methods

The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and multivariate Cox analysis. Receiver operating characteristic (ROC) curve was used to evaluate the five-mRNA signature in pediatric Wilms tumor patients. Bootstrap test with 500 times was used to perform the internal validation.

Results

We identified 6,964 differentially expressed mRNAs associated with pediatric WT, including 3,190 downregulated mRNAs and 3,774 up-regulated mRNAs. Univariate and multivariate Cox analysis identified five mRNAs (SPRY1, SPIN4, MAP7D3, C10orf71, and SPAG11A) to establish a predictive model. The risk score formula is as follows: Risk score = 0.3036*SPIN4 + 0.8576*MAP7D3 -0.1548*C10orf71 -0.7335*SPRY1 -0.2654*SPAG11A. The pediatric WT patients were divided into low-risk group and high-risk group based on the median risk score (value = 1.1503). The receiver operating characteristic (ROC) curve analysis revealed good performance of the 5-mRNA prognostic model (the area under the curve [AUC] was 0.821). Bootstrap test (Bootstrap resampling times = 500) was used to perform the internal validation and revealed that the AUC was 0.822. REACTOME, KEGG, and BIOCARTA pathway analyses demonstrated that these survival-related genes were mainly enriched in ErbB2 and ErbB3 signaling pathways, and calcium signaling pathway.

Conclusion

The five-mRNA signature can predict the prognosis of patients with pediatric WT. It has significant implication in the understanding of therapeutic targets for pediatric WT patients. However, further study is needed to validate this five-mRNA signature and uncover more novel diagnostic or prognostic mRNAs candidates in pediatric WT patients.

SUBMITTER: Lin XD

PROVIDER: S-EPMC6978231 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of a five-mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor.

Lin Xiao-Dan XD Wu Yu-Peng YP Chen Shao-Hao SH Sun Xiong-Lin XL Ke Zhi-Bin ZB Chen Dong-Ning DN Li Xiao-Dong XD Lin Yun-Zhi YZ Wei Yong Y Zheng Qing-Shui QS Xu Ning N Xue Xue-Yi XY

Molecular genetics & genomic medicine 20191107 1

<h4>Background</h4>The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT).<h4>Methods</h4>The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and mu ...[more]

PMID: 31701684

Similar Datasets

Project description:Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low (P = 0.0018) and high (P = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b (P = 0.0027 and P = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed in situ hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were WTX (47%), IGF2 (21%), 1q (36%) gain, 1p36 (16%), and WTX deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.

Project description:Mounting evidence has demonstrated that a lot of miRNAs are overexpressed or downregulated in colorectal cancer (CRC) tissues and play a crucial role in tumorigenesis, invasion, and migration. The aim of our study was to screen new biomarkers related to CRC prognosis by bioinformatics analysis. By using the R language edgeR package for the differential analysis and standardization of miRNA expression profiles from The Cancer Genome Atlas (TCGA), 502 differentially expressed miRNAs (343 up-regulated, 159 down-regulated) were screened based on the cut-off criteria of p < 0.05 and |log2FC|>1, then all the patients (421) with differentially expressed miRNAs and complete survival time, status were then randomly divided into train group (212) and the test group (209). Eight miRNAs with p < 0.005 were revealed in univariate cox regression analysis of train group, then stepwise multivariate cox regression was applied for constituting a five-miRNA (hsa-miR-5091, hsa-miR-10b-3p, hsa-miR-9-5p, hsa-miR-187-3p, hsa-miR-32-5p) signature prognostic biomarkers with obviously different overall survival. Test group and entire group shown the same results utilizing the same prescient miRNA signature. The area under curve (AUC) of receiver operating characteristic (ROC) curve for predicting 5 years survival in train group, test group, and whole cohort were 0.79, 0.679, and 0.744, respectively, which demonstrated better predictive power of prognostic model. Furthermore, Univariate cox regression and multivariate cox regression considering other clinical factors displayed that the five-miRNA signature could serve as an independent prognostic factor. In order to predict the potential biological functions of five-miRNA signature, target genes of these five miRNAs were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) enrichment analysis. The top 10 hub genes (ESR1, ADCY9, MEF2C, NRXN1, ADCY5, FGF2, KITLG, GATA1, GRIA1, KAT2B) of target genes in protein protein interaction (PPI) network were screened by string database and Cytoscape 3.6.1 (plug-in cytoHubba). In addition, 19 of target genes were associated with survival prognosis. Taken together, the current study showed the model of five-miRNA signature could efficiently function as a novel and independent prognosis biomarker and therapeutic target for CRC patients.

Dataset Information

Identification of a five-mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor.

Background

Methods

Results

Conclusion

Publications

Identification of a five-mRNA signature as a novel potential prognostic biomarker in pediatric Wilms tumor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets