Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment
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 p...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222400180X |
| _version_ | 1797248406143369216 |
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| author | Sara Salvador-Martín Gianluca Rubbini Perceval Vellosillo Paula Zapata-Cobo Marta Velasco Laura M. Palomino Susana Clemente Oscar Segarra Ana Moreno-Álvarez Ana Fernández-Lorenzo Begoña Pérez-Moneo Montserrat Montraveta Cesar Sánchez Mar Tolín Inés Loverdos María José Fobelo Victor Manuel Navas-López Lorena Magallares Ruth García-Romero Ricardo Torres-Peral Alejandro Rodríguez Ferrán Bossacoma Vicente Merino-Bohórquez Enrique Salcedo Rebeca Álvarez Ana Dopazo María Sanjurjo-Sáez Luis A. López-Fernández |
| author_facet | Sara Salvador-Martín Gianluca Rubbini Perceval Vellosillo Paula Zapata-Cobo Marta Velasco Laura M. Palomino Susana Clemente Oscar Segarra Ana Moreno-Álvarez Ana Fernández-Lorenzo Begoña Pérez-Moneo Montserrat Montraveta Cesar Sánchez Mar Tolín Inés Loverdos María José Fobelo Victor Manuel Navas-López Lorena Magallares Ruth García-Romero Ricardo Torres-Peral Alejandro Rodríguez Ferrán Bossacoma Vicente Merino-Bohórquez Enrique Salcedo Rebeca Álvarez Ana Dopazo María Sanjurjo-Sáez Luis A. López-Fernández |
| author_sort | Sara Salvador-Martín |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T22:01:02Z |
| format | Article |
| id | doaj.art-4b0faa08ee99409eb3ae49564d84206d |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:14:05Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-4b0faa08ee99409eb3ae49564d84206d2024-03-23T06:22:41ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-04-01173116299Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatmentSara Salvador-Martín0Gianluca Rubbini1Perceval Vellosillo2Paula Zapata-Cobo3Marta Velasco4Laura M. Palomino5Susana Clemente6Oscar Segarra7Ana Moreno-Álvarez8Ana Fernández-Lorenzo9Begoña Pérez-Moneo10Montserrat Montraveta11Cesar Sánchez12Mar Tolín13Inés Loverdos14María José Fobelo15Victor Manuel Navas-López16Lorena Magallares17Ruth García-Romero18Ricardo Torres-Peral19Alejandro Rodríguez20Ferrán Bossacoma21Vicente Merino-Bohórquez22Enrique Salcedo23Rebeca Álvarez24Ana Dopazo25María Sanjurjo-Sáez26Luis A. López-Fernández27Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Unidad de Investigación Materno Infantil Fundación Familia Alonso (UDIMIFFA), SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainHospital Universitario Infantil Niño Jesús, Madrid, SpainHospital Universitario Infantil Niño Jesús, Madrid, SpainHospital Vall d′Hebrón, Barcelona, SpainHospital Vall d′Hebrón, Barcelona, SpainHospital Universitario A Coruña, A Coruña, SpainHospital Universitario A Coruña, A Coruña, SpainHospital Universitario Infanta Leonor, Madrid, SpainHospital Universitario Germans Trias i Pujol, Badalona, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainHospital Universitario Parc Taulí, Sabadell, SpainHospital Universitario Virgen de Valme, Universidad de Sevilla, Sevilla, SpainHospital Regional Universitario de Málaga, SpainHospital Universitario la Paz, Madrid, SpainHospital Universitario Miguel Servet, Zaragoza, SpainComplejo Asistencial Universitario de Salamanca, Salamanca, SpainHospital Universitario Virgen del Rocio, Sevilla, SpainServicio de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Dèu, Barcelona, SpainHospital Universitario Virgen de la Macarena, Universidad de Sevilla, Sevilla, SpainHospital Universitario Doce de Octubre, Madrid, SpainGenomics Unit, Spanish National Center for Cardiovascular Disease (CNIC), Madrid 28029, SpainGenomics Unit, Spanish National Center for Cardiovascular Disease (CNIC), Madrid 28029, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S075333222400180XRNA-seqPharmacogenomicsInflammatory bowel diseaseAnti-TNF drugsPediatrics |
| spellingShingle | Sara Salvador-Martín Gianluca Rubbini Perceval Vellosillo Paula Zapata-Cobo Marta Velasco Laura M. Palomino Susana Clemente Oscar Segarra Ana Moreno-Álvarez Ana Fernández-Lorenzo Begoña Pérez-Moneo Montserrat Montraveta Cesar Sánchez Mar Tolín Inés Loverdos María José Fobelo Victor Manuel Navas-López Lorena Magallares Ruth García-Romero Ricardo Torres-Peral Alejandro Rodríguez Ferrán Bossacoma Vicente Merino-Bohórquez Enrique Salcedo Rebeca Álvarez Ana Dopazo María Sanjurjo-Sáez Luis A. López-Fernández Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment Biomedicine & Pharmacotherapy RNA-seq Pharmacogenomics Inflammatory bowel disease Anti-TNF drugs Pediatrics |
| title | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| title_full | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| title_fullStr | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| title_full_unstemmed | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| title_short | Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| title_sort | blood gene expression biomarkers of response to anti tnf drugs in pediatric inflammatory bowel diseases before initiation of treatment |
| topic | RNA-seq Pharmacogenomics Inflammatory bowel disease Anti-TNF drugs Pediatrics |
| url | http://www.sciencedirect.com/science/article/pii/S075333222400180X |
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