DIFFERENTIAL GENE EXPRESSION ANALYSIS IN NON-MUSCLE INVASIVE BLADDER CANCER

Karoline Brito Caetano Andrade Coelho; Natalia Alonso-Moreda; Dalila L Zanette; Javier De Las Rivas; Rodolfo Borges dos Reis

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Paper Title

DIFFERENTIAL GENE EXPRESSION ANALYSIS IN NON-MUSCLE INVASIVE BLADDER CANCER

Authors

Karoline Brito Caetano Andrade Coelho
Natalia Alonso-Moreda
Dalila L Zanette
Javier De Las Rivas
Rodolfo Borges dos Reis

Modality

Poster

Subject area

RNA and transcriptomics

Publishing Date

21/11/2024

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting-2024/832426-differential-gene-expression-analysis-in-non-muscle-invasive-bladder-cancer

ISBN

978-65-272-0843-3

Keywords

Non-muscle invasive, Bladder cancer, Recurrence, Gene Expression, Urine, Tumor

Summary

Non-muscle-invasive bladder cancer (NMIBC) represents 75% of the cases and has a high recurrence rate. These patients require frequent follow-up and the current diagnosis and surveillance methods still present challenges. Despite noninvasive biomarkers being approved by the FDA, none have been incorporated into current clinical practice. In this way, using gene expression profiling we aim to identify urinary biomarkers panel that may indicate aggressiveness in NMIBC. In this study, we used microarray and RNA-seq-based data from the Gene Expression Omnibus repository to carry out differential gene expression (DGE) analyses. The GSE31189 dataset included the expression of 92 saline bladder barbotage samples using the Affymetrix Human Genome U133 Plus 2.0 microarrays platform, by comparison of 52 samples of human urothelial cancer cells versus 40 samples of human non-cancer urothelial cells. In brief, we performed a similar workflow to the one proposed by the GEO2R, using GEOquery and limma to perform the DGE analysis for array data, with a previous normalization using the affy package from Bioconductor, and mapping the probes to genes with the method GateExplorer. On the other hand, the second dataset (GSE163899) included samples tested with RNA-seq expression using the HiSeq 2500 (Illumina) by comparison of 15 tumor samples from NMIBC patients with non-relapse versus 9 samples of NMIBC patients experiencing recurrence. The raw counts of the samples were introduced in the algorithm Limma-Voom to perform the statistical analysis and find the genes with significant differential expression. In addition, the WEB-based Gene Set Analysis Toolkit (WebGestalt) tool was used for functional enrichment analysis of the DEgenes. A total of 484 differentially expressed genes were identified in the GSE31189 after normalization (263 upregulated and 221 downregulated in between human urothelial cancer cells). The functional analysis displayed a strong association of the 263 mRNA upregulated with immune and defense response by the presence of multiple cytokines and signals of leukocytes, revealed by the overexpression of mRNA like CXCL2, CXCL8, and IL1B. Considering the signature of 484 DEgenes, the genes with p.value<0.01 and log2FC>0.5 or <-0.5 were selected to generate the heatmap plot. The results indicated 7 genes (SRD5A2, CAPN8, REN, MYBPC1, PALM3, UPK3A, SCUBE2) downregulated in human urothelial cancer cells. We identified a signature comprising 1449 differentially expressed genes from NMIBC tumors (GSE163899). After, filtering to leave only the genes with p.value<0.05 and log2FC>1.0 or <-1.0 we found 239 genes upregulated in non-relapse and 308 genes upregulated in recurrence. Pathways associated with cytokine-mediated signaling, defense, and immune response, with a particular molecular response to type I interferon (with genes IFI6, IFI27, IFI35) were markedly upregulated in NMIBC non-relapse. We also selected the genes with p.value<0.01 and logFC>1.75 or <-1.75 to generate the heatmap plot. The data displayed 41 upregulated in non-relapse and 42 upregulated in recurrence genes. These data increase our understanding of the non-relapse and the recurrence in NMIBC tumors and suggest that part of aggressiveness may be explained by a lack of efficient defense and immune response.

Title of the Event: 20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event: Salvador
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

COELHO, Karoline Brito Caetano Andrade et al.. DIFFERENTIAL GENE EXPRESSION ANALYSIS IN NON-MUSCLE INVASIVE BLADDER CANCER.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/832426-DIFFERENTIAL-GENE-EXPRESSION-ANALYSIS-IN-NON-MUSCLE-INVASIVE-BLADDER-CANCER. Access in: 19/05/2025