Artículo
Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment
Autor/es | Salvador-Martín, Sara
Rubbini, Gianluca Vellosillo, Perceval Zapata Cobo, Paula Velasco, Marta Palomino, Laura M. Clemente, Susana Segarra, Oscar Merino Bohórquez, Vicente ![]() ![]() ![]() ![]() ![]() ![]() López Fernández, Luis Andrés |
Departamento | Universidad de Sevilla. Departamento de Farmacología |
Fecha de publicación | 2024 |
Fecha de depósito | 2024-06-05 |
Publicado en |
|
Resumen | 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 ... 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. |
Agencias financiadoras | Instituto de Salud Carlos III Comunidad Autónoma de Madrid |
Identificador del proyecto | PI19/00792
![]() PI22/00584 ![]() PEJ-2021-AI/BMD-21866 ![]() PIPF2022/SAL-GL-24790 ![]() |
Cita | 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. |
Ficheros | Tamaño | Formato | Ver | Descripción |
---|---|---|---|---|
Blood gene expression_Merino.pdf | 4.670Mb | ![]() | Ver/ | |