dc.creator | Salvador-Martín, Sara | es |
dc.creator | Rubbini, Gianluca | es |
dc.creator | Vellosillo, Perceval | es |
dc.creator | Zapata Cobo, Paula | es |
dc.creator | Velasco, Marta | es |
dc.creator | Palomino, Laura M. | es |
dc.creator | Clemente, Susana | es |
dc.creator | Segarra, Oscar | es |
dc.creator | Merino Bohórquez, Vicente | es |
dc.creator | López Fernández, Luis Andrés | es |
dc.date.accessioned | 2024-06-05T11:26:13Z | |
dc.date.available | 2024-06-05T11:26:13Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Salvador-Martín, S., Rubbini, G., Vellosillo, P., Zapata Cobo, P., Velasco, M., Palomino, L.M.,...,López Fernández, L.A. (2024). Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment. Biomedicine & Pharmacotherapy, 173, 116299. https://doi.org/10.1016/j.biopha.2024.116299. | |
dc.identifier.issn | 1950-6007 (electrónico) | es |
dc.identifier.issn | 0753-3322 (impreso) | es |
dc.identifier.uri | https://hdl.handle.net/11441/159770 | |
dc.description.abstract | Background/aims: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.Methods: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Results: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). Conclusions: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs. | es |
dc.description.sponsorship | Instituto de Salud Carlos III (ISCIII) PI19/00792 and PI22/00584 | es |
dc.description.sponsorship | Comunidad Autónoma de Madrid PEJ-2021-AI/BMD-21866 and PIPF2022/SAL-GL-24790 | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | es |
dc.relation.ispartof | Biomedicine & Pharmacotherapy, 173, 116299. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | RNA-seq | es |
dc.subject | Pharmacogenomics | es |
dc.subject | Inflammatory bowel disease | es |
dc.subject | Anti-TNF drugs | es |
dc.subject | Pediatrics | es |
dc.title | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Farmacología | es |
dc.relation.projectID | PI19/00792 | es |
dc.relation.projectID | PI22/00584 | es |
dc.relation.projectID | PEJ-2021-AI/BMD-21866 | es |
dc.relation.projectID | PIPF2022/SAL-GL-24790 | es |
dc.relation.publisherversion | https://doi.org/10.1016/j.biopha.2024.116299 | es |
dc.identifier.doi | 10.1016/j.biopha.2024.116299 | es |
dc.journaltitle | Biomedicine & Pharmacotherapy | es |
dc.publication.volumen | 173 | es |
dc.publication.initialPage | 116299 | es |
dc.contributor.funder | Instituto de Salud Carlos III | es |
dc.contributor.funder | Comunidad Autónoma de Madrid | es |