Dataset Information

Comprehensive Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms' Tumor.

ABSTRACT: Wilms' tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progression. So far, their roles and related competitive endogenous RNA (ceRNA) network remain unelucidated in nephroblastoma pathogenesis. We comprehensively integrated lncRNA, microRNA (miRNA), and messenger RNA (mRNA) expression profiles from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and screened out differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network based on the information generated from miRcode, miRTarBase, TargetScan, and miRDB. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to analyze the functional characteristics of DEMs in the ceRNA network. The interaction between protein molecules was also analyzed by establishing a protein-protein interaction network. Finally, prognosis-related biomarkers were identified via survival analysis. Initially, 1647 DELs, 115 DEMis, and 3280 DEMs (|log FC|?>?2; FDR?

SUBMITTER: Zheng H

PROVIDER: S-EPMC7057018 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms' Tumor.

Zheng Hong H Li Bai-Hui BH Liu Chang C Jia Li L Liu Feng-Ting FT

BioMed research international 20200221

Wilms' tumor (WT) is the most common type of childhood kidney cancer, and most cases present with favorable histology and respond well to standard treatment. However, a subset of patients with WT is diagnosed with bilateral, relapsed, and high-risk tumors which remain the leading cause of cancer-related death in children. Long noncoding RNAs (lncRNAs) and their aberrant expression have currently been attracting great attention as oncogenes or tumor suppressors during tumor initiation and progres ...[more]

PMID: 32149111

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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.

Dataset Information

Comprehensive Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms' Tumor.

Publications

Comprehensive Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Biomarkers in Wilms' Tumor.

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