Bioinformatics analysis and identification of genes and pathways involved in patients with Wilms tumor.

Background: Wilms tumor is the most common childhood kidney malignant tumor. However, the genes and signaling pathways associated with the disease remain incompletely understood. Methods: GSE66405, GSE73209, and GSE11151 were collected from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were detected using R software. A protein-protein interaction (PPI) network was constructed using the STRING database, and the clustering modules and hub genes were analyzed with the Cytoscape software. Genes functional enrichment analyses were performed using the package "clusterProfiler" in R software, and the gene set enrichment analysis (GSEA) analysis was performed using GSEA v4.1.0 software. Results: Respectively, 3,092, 620, and 3,567 DEGs were screened in GSE66405, GSE73209, and GSE11151, with a total of 474 common DEGs detected in three expression profiles. For the common DEGs, the top 30 significant results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were presented. Furthermore, five modules were found as the most related modules to Wilms tumor. GO term and KEGG pathway enrichment analyses of the genes in all the modules identified 10 GO terms and 5 KEGG pathways as significantly enriched. The top 10 hub DEGs of the PPI network were ALB, CDH1, EGF, AQP2, REN, SLC2A2, SPP1, UMOD, NPHS2, and FOXM1, with ALB identified as the highest degree. GSEA results showed 11 pathways were correlated with ALB expression in GSE66405 and 10 pathways were related to the expression of the ALB gene in GSE73209. Conclusions: Our study revealed robust gene signatures in Wilms tumor. Dysregulations of the signaling pathways were associated with the development and progression of the Wilms tumor, and 10 hub genes may play important roles in its diagnosis and therapy.

Erratum to comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms' tumor.

[This corrects the article DOI: 10.21037/atm-20-6047.].

Comprehensive bioinformatics analysis of the TP53 signaling pathway in Wilms' tumor.

BACKGROUND: Differential expression of tumor protein 53 (TP53, or p53) has been observed in multiple cancers. However, the expression levels and prognostic role of TP53 signaling pathway genes in Wilms' tumor (WT) have yet to be fully explored. METHODS: The expression levels of TP53 signaling pathway genes including TP53, mouse double minute 2 (MDM2), mouse double minute 4 (MDM4), cyclin-dependent kinase 2A (CDKN2A), cyclin-dependent kinase 2B (CDKN2B), and tumor suppressor p53-binding protein 1 (TP53BP1) in WT were analyzed using the Oncomine database. Aberration types, co-mutations, mutation locations, signaling pathways, and the prognostic role of TP53 in WT were investigated using cBioPortal. MicroRNA (miRNA) and transcription factor (TF) targets were identified with miRTarBase, miWalk, and ChIP-X Enrichment Analysis 3 (CheA3), respectively. A protein-protein network was constructed using GeneMANIA. The expression of TP53 signaling genes were confirmed in WT samples and normal kidney tissues using the Human Protein Atlas (HPA). Cancer Therapeutics Response Portal (CTRP) was used to analyze the small molecules potentially targeting TP53. RESULTS: TP53 was significantly expressed in the Cutcliffe Renal (P=0.010), but not in the Yusenko Renal (P=0.094). Meanwhile, MDM2 was significantly overexpressed in the Yusenko Renal (P=0.058), but not in the Cutcliffe Renal (P=0.058). The expression levels of MDM4 no significant difference between the tumor and normal tissue samples. The most common TP53 alteration was missense and the proportion of TP53 pathway-related mutations was 2.3%. Co-expressed genes included ZNF609 (zinc finger protein 609), WRAP53 (WD40-encoding RNA antisense to p53), CNOT2 (CC chemokine receptor 4-negative regulator of transcription 2), and CDH13 (cadherin 13). TP53 alterations indicated poor prognosis of WT (P=1.051e-4). The regulators of the TP53 pathway included miR-485-5p and TFs NR2F2 and KDM5B. The functions of TP53 signaling pathway were signal transduction in response to DNA damage and regulate the cell cycle. The small molecules targeting TP53 included PRIMA-1, RITA, SJ-172550, and SCH-529074. CONCLUSIONS: TP53 was found to be differentially expressed in WT tissues. TP53 mutations indicated poor outcomes of WT. Therefore, pifithrin-mu, PRIMA-1, RITA, SJ-172550, and SCH-529074 could be used in combination with traditional chemotherapy to treat WT.

Comparative genomics of Toll-like receptor signalling in five species.

BACKGROUND: Over the last decade, several studies have identified quantitative trait loci (QTL) affecting variation of immune related traits in mammals. Recent studies in humans and mice suggest that part of this variation may be caused by polymorphisms in genes involved in Toll-like receptor (TLR) signalling. In this project, we used a comparative approach to investigate the importance of TLR-related genes in comparison with other immunologically relevant genes for resistance traits in five species by associating their genomic location with previously published immune-related QTL regions. RESULTS: We report the genomic localisation of TLR1-10 and ten associated signalling molecules in sheep and pig using in-silico and/or radiation hybrid (RH) mapping techniques and compare their positions with their annotated homologues in the human, cattle and mouse whole genome sequences. We also report medium-density RH maps for porcine chromosomes 8 and 13. A comparative analysis of the positions of previously published relevant QTLs allowed the identification of homologous regions that are associated with similar health traits in several species and which contain TLR related and other immunologically relevant genes. Additional evidence was gathered by examining relevant gene expression and association studies. CONCLUSION: This comparative genomic approach identified eight genes as potentially causative genes for variations of health related traits. These include susceptibility to clinical mastitis in dairy cattle, general disease resistance in sheep, cattle, humans and mice, and tolerance to protozoan infection in cattle and mice. Four TLR-related genes (TLR1, 6, MyD88, IRF3) appear to be the most likely candidate genes underlying QTL regions which control the resistance to the same or similar pathogens in several species. Further studies are required to investigate the potential role of polymorphisms within these genes.

Expression screening and annotation of a zebrafish myoblast cDNA library.

To analyse the myogenic transcriptome and identify novel genes involved in muscle development in an in vivo context, we have constructed a muscle specific cDNA library from GFP-expressing myoblasts purified by fluorescent activated cell sorting of transgenic zebrafish embryos. We have generated 153,428 EST sequences from this library that have been clustered into consensi, mapped to the genome assembly Zv6 and analysed for protein homology. Expression analysis of a randomly picked sample of clones using whole mount in situ hybridisation, identified 30 genes that are expressed specifically within the myotome, one third of which represent novel sequences. These genes have been assigned to syn-expression groups. The sequencing of the myoblast enriched cDNA library has significantly increased the number of zebrafish ESTs, facilitating the prediction of new spliced transcripts in the genome assembly and providing a transcriptome of an in vivo myoblast cell.

Transcriptome analysis for the chicken based on 19,626 finished cDNA sequences and 485,337 expressed sequence tags.

We present an analysis of the chicken (Gallus gallus) transcriptome based on the full insert sequences for 19,626 cDNAs, combined with 485,337 EST sequences. The cDNA data set has been functionally annotated and describes a minimum of 11,929 chicken coding genes, including the sequence for 2260 full-length cDNAs together with a collection of noncoding (nc) cDNAs that have been stringently filtered to remove untranslated regions of coding mRNAs. The combined collection of cDNAs and ESTs describe 62,546 clustered transcripts and provide transcriptional evidence for a total of 18,989 chicken genes, including 88% of the annotated Ensembl gene set. Analysis of the ncRNAs reveals a set that is highly conserved in chickens and mammals, including sequences for 14 pri-miRNAs encoding 23 different miRNAs. The data sets described here provide a transcriptome toolkit linked to physical clones for bioinformaticians and experimental biologists who wish to use chicken systems as a low-cost, accessible alternative to mammals for the analysis of vertebrate development, immunology, and cell biology.