TY - JOUR
T1 - Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment
AU - Salvador-Martín, Sara
AU - Rubbini, Gianluca
AU - Vellosillo, Perceval
AU - Zapata-Cobo, Paula
AU - Velasco, Marta
AU - Palomino, Laura M
AU - Clemente, Susana
AU - Segarra, Oscar
AU - Moreno-Álvarez, Ana
AU - Fernández-Lorenzo, Ana
AU - Pérez-Moneo, Begoña
AU - Montraveta, Montserrat
AU - Sánchez, Cesar
AU - Tolín, Mar
AU - Loverdos, Inés
AU - Fobelo, María José
AU - Navas-López, Víctor Manuel
AU - Magallares, Lorena
AU - García-Romero, Ruth
AU - Torres-Peral, Ricardo
AU - Rodríguez, Alejandro
AU - Bossacoma, Ferrán
AU - Merino-Bohórquez, V.
AU - Salcedo, Enrique
AU - Álvarez, Rebeca
AU - Dopazo, Ana
AU - Sanjurjo-Sáez, María
AU - López-Fernández, Luis A.
N1 - Publisher Copyright:
© 2024
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - RNA-seq Pharmacogenomics Inflammatory bowel disease Anti-TNF drugs Pediatrics
UR - http://www.scopus.com/inward/record.url?scp=85185783437&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/a03a0ed8-30de-34ff-bf33-4e3e1a3ba839/
M3 - Article
C2 - 38401525
SN - 0753-3322
VL - 173
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 116299
ER -
