Dataset Information

Integrative Transcriptomic Profiling of the Wilms Tumor.

ABSTRACT: Our study aimed to identify relevant transcriptomic biomarkers for the Wilms tumor, the most common pediatric kidney cancer, independent of the histological type and stage. Using next-generation sequencing, we analyzed the miRNA profiles of 74 kidney samples, which were divided into two independent groups: fresh frozen tissue and formalin-fixed paraffin-embedded tissue samples. Subsequent mRNA expression profiling and pathway analysis were performed to establish the interplay and potential involvement of miRNAs and mRNA in the Wilms tumor. Comparative analysis, irrespective of post-dissection tissue processing, revealed 41 differentially expressed miRNAs, with 27 miRNAs having decreased expression and 14 miRNAs having increased expression in the Wilms tumor tissue compared to healthy kidney tissue. Among global mRNA transcriptomic profile differences, cross-sectional analysis suggested a limited list of genes potentially regulated by differentially expressed miRNAs in the Wilms tumor. This study identified the comprehensive miRNA and mRNA profile of the Wilms tumor using next-generation sequencing and bioinformatics approach, providing better insights into the pathogenesis of the Wilms tumor. The identified Wilms tumor miRNAs have potential as biomarkers for the diagnosis and treatment of the Wilms tumor, regardless of histological subtype and disease stage.

SUBMITTER: Avcin SL

PROVIDER: S-EPMC10416970 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative Transcriptomic Profiling of the Wilms Tumor.

Avčin Simona Lucija SL Črepinšek Klementina K Jenko Bizjan Barbara B Šket Robert R Kovač Jernej J Vrhovšek Blaž B Blazina Jerca J Blatnik Olga O Kordič Robert R Kitanovski Lidija L Jazbec Janez J Debeljak Maruša M Tesovnik Tine T

Cancers 20230728 15

Our study aimed to identify relevant transcriptomic biomarkers for the Wilms tumor, the most common pediatric kidney cancer, independent of the histological type and stage. Using next-generation sequencing, we analyzed the miRNA profiles of 74 kidney samples, which were divided into two independent groups: fresh frozen tissue and formalin-fixed paraffin-embedded tissue samples. Subsequent mRNA expression profiling and pathway analysis were performed to establish the interplay and potential invol ...[more]

PMID: 37568662

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:Wilms tumor (WT) is a pediatric kidney cancer associated with poor outcomes in patients with unfavorable histological features such as anaplasia. Small non-coding RNAs, such as miRNAs, are known to be involved in WT pathogenesis. However, research on the clinical potential of blood-based miRNAs is limited. This study aimed to profile aberrantly expressed miRNAs in WT serum samples, evaluate their potential to differentiate standard-risk patients with favorable histology from those with anaplastic WTs, and assess their clinical value as minimally invasive biomarkers for WT detection. The study used next-generation sequencing (NGS) to analyze miRNA expressions in serum samples from 37 Egyptian children, including 10 healthy individuals, 14 with non-anaplastic WTs (favorable histology FH-WTs), and 13 with anaplastic WTs (unfavorable histology UnFH-WTs). Functional enrichment analysis was conducted to identify critical pathways and biological processes affected by dysregulated miRNAs, and a network was created for the most promising miRNA-target interactions linked to WT. The study identified a distinct miRNA expression signature of 45 miRNAs (3 upregulated and 42 downregulated) in WT serum samples compared to healthy controls, with 29 miRNAs exclusively dysregulated in FH-WTs and 6 miRNAs dysregulated solely in UnFH-WTs. These dysregulated miRNAs displayed significant enrichment in cancer-related pathways, such as PI3K/AKT, FOXO, and MAPK signaling. In relation to WT clinicopathological features, decreased levels of hsa-miR-2355-3p showed a significant positive correlation with clinical stage (r = 0.6597, p = 0.0006) and WT metastasis (r = 0.439, p = 0.021). The ROC curve analysis revealed that multiple dysregulated miRNAs in WT, specifically hsa-miR-7-5p, hsa-miR-146a-5p, hsa-miR-378a-3p, and hsa-miR-483-5p, exhibited high diagnostic potential for WT, with AUC values exceeding 0.86. Among WT histopathology types, the hsa-miR-1180-3p showed a 2.3 log2fold difference in expression between UnFH-WTs and FH-WTs, indicating its potential as a biomarker with 92% sensitivity and 85% specificity for identifying UnFH-WTs. Its target genes were enriched in pathways related to cell division and cell cycle regulation. In conclusion, hsa-miR-1180-3p could be a reliable blood-based biomarker for distinguishing WT histopathological types, and further research is needed to validate its clinical value.

Dataset Information

Integrative Transcriptomic Profiling of the Wilms Tumor.

Publications

Integrative Transcriptomic Profiling of the Wilms Tumor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets