Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis
ABSTRACT Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton‐pump inhibitors (PPI) induce disease remission but no predictive factors of PPI‐responsiveness have been identified yet. So, a biomarker must be found to differentia...
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| Veröffentlicht in: | Journal of pediatric gastroenterology and nutrition 2020-12, Vol.71 (6), p.755-763 |
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| creator | Cañas, José Antonio Tabares, Ana Barbero, Claudia García‐Sánchez, Daniel Sastre, Beatriz Rodrigo‐Muñoz, José Manuel Mahíllo‐Fernández, Ignacio Rayo, Ana Borrell, Belén Cilleruelo, Mª Luz Román, Enriqueta Fernandez‐Fernandez, Sonia Gutiérrez‐Junquera, Carolina Pozo, Victoria |
| description | ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton‐pump inhibitors (PPI) induce disease remission but no predictive factors of PPI‐responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI‐R) and nonresponder patients (PPI‐NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.
Methods:
This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI‐R or PPI‐NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.
Results:
We found several esophageal miRNAs with different expression values between PPI‐R and PPI‐NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI‐R displayed a significant decrease in eotaxin‐3, IL‐5, IL‐13, periostin, and major basic protein (P |
| doi_str_mv | 10.1097/MPG.0000000000002957 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7752232</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2448410407</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5567-dbd5d76dfa4d73d522890e9415144f6e12cfc740b1a28d10e61921ec5adff0683</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EokPhDRDKkk2Kr2PHyQKkdjT9QaWMKiqWlid2JgbHDnZC1R2P0GfkSfBoplVhAViyrCt_51z7HoReAj4AXPM3H5YnB_jBIjXjj9AMWFHmtMLwGM0w4TwnAOUeehbjlwRxyvBTtFcUGBdQ0hkalsGP3v38cTtM_ZCduc6szOhDdqnj4F3U2TJoZZrReJddRePW2SL6oZNrLW3Wmyb4y4vDmBmXzTtjVdAu-2zGLlv4BCfQWNPcScxo4nP0pJU26he7cx9dHS8-zU_z848nZ_PD87xhrOS5WimmeKlaSRUvFCOkqrGuKTCgtC01kKZtOMUrkKRSgHUJNQHdMKnaFpdVsY_ebX2HadVr1Wg3BmnFEEwvw43w0ojfb5zpxNp_F5ynZgVJBq93BsF_m3QcRW9io62VTvspCkJpRQFTzBNKt2iaRoxBt_dtAItNWCKFJf4MK8lePXzivegunQRUW-Da21GH-NVO1zqILo1-7P7lTf8i3WAMeJkTTDCQVOVpw6bj253MWH3zX98Q75cXxdExJkBZ8QtNS8VG</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2448410407</pqid></control><display><type>article</type><title>Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Cañas, José Antonio ; Tabares, Ana ; Barbero, Claudia ; García‐Sánchez, Daniel ; Sastre, Beatriz ; Rodrigo‐Muñoz, José Manuel ; Mahíllo‐Fernández, Ignacio ; Rayo, Ana ; Borrell, Belén ; Cilleruelo, Mª Luz ; Román, Enriqueta ; Fernandez‐Fernandez, Sonia ; Gutiérrez‐Junquera, Carolina ; Pozo, Victoria</creator><creatorcontrib>Cañas, José Antonio ; Tabares, Ana ; Barbero, Claudia ; García‐Sánchez, Daniel ; Sastre, Beatriz ; Rodrigo‐Muñoz, José Manuel ; Mahíllo‐Fernández, Ignacio ; Rayo, Ana ; Borrell, Belén ; Cilleruelo, Mª Luz ; Román, Enriqueta ; Fernandez‐Fernandez, Sonia ; Gutiérrez‐Junquera, Carolina ; Pozo, Victoria</creatorcontrib><description>ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton‐pump inhibitors (PPI) induce disease remission but no predictive factors of PPI‐responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI‐R) and nonresponder patients (PPI‐NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.
Methods:
This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI‐R or PPI‐NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.
Results:
We found several esophageal miRNAs with different expression values between PPI‐R and PPI‐NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI‐R displayed a significant decrease in eotaxin‐3, IL‐5, IL‐13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).
Conclusions:
Esophageal miRNA levels found are able to discriminate between both PPI‐R and PPI‐NR at baseline, and before and after treatment in PPI‐R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI‐R patients after PPI therapy.</description><identifier>ISSN: 0277-2116</identifier><identifier>EISSN: 1536-4801</identifier><identifier>DOI: 10.1097/MPG.0000000000002957</identifier><identifier>PMID: 33003164</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Biomarkers - analysis ; Child ; eosinophilic esophagitis ; Eosinophilic Esophagitis - drug therapy ; Eosinophilic Esophagitis - genetics ; esophagus ; Humans ; Male ; microRNA ; MicroRNAs - metabolism ; Original : Gastroenterology: Eosinophilic GI Disease ; Prospective Studies ; Proton Pump Inhibitors - therapeutic use ; proton‐pump inhibitor ; responsiveness</subject><ispartof>Journal of pediatric gastroenterology and nutrition, 2020-12, Vol.71 (6), p.755-763</ispartof><rights>2020 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition</rights><rights>Lippincott Williams & Wilkins</rights><rights>2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology</rights><rights>Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5567-dbd5d76dfa4d73d522890e9415144f6e12cfc740b1a28d10e61921ec5adff0683</citedby><cites>FETCH-LOGICAL-c5567-dbd5d76dfa4d73d522890e9415144f6e12cfc740b1a28d10e61921ec5adff0683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1097%2FMPG.0000000000002957$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1097%2FMPG.0000000000002957$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33003164$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cañas, José Antonio</creatorcontrib><creatorcontrib>Tabares, Ana</creatorcontrib><creatorcontrib>Barbero, Claudia</creatorcontrib><creatorcontrib>García‐Sánchez, Daniel</creatorcontrib><creatorcontrib>Sastre, Beatriz</creatorcontrib><creatorcontrib>Rodrigo‐Muñoz, José Manuel</creatorcontrib><creatorcontrib>Mahíllo‐Fernández, Ignacio</creatorcontrib><creatorcontrib>Rayo, Ana</creatorcontrib><creatorcontrib>Borrell, Belén</creatorcontrib><creatorcontrib>Cilleruelo, Mª Luz</creatorcontrib><creatorcontrib>Román, Enriqueta</creatorcontrib><creatorcontrib>Fernandez‐Fernandez, Sonia</creatorcontrib><creatorcontrib>Gutiérrez‐Junquera, Carolina</creatorcontrib><creatorcontrib>Pozo, Victoria</creatorcontrib><title>Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis</title><title>Journal of pediatric gastroenterology and nutrition</title><addtitle>J Pediatr Gastroenterol Nutr</addtitle><description>ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton‐pump inhibitors (PPI) induce disease remission but no predictive factors of PPI‐responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI‐R) and nonresponder patients (PPI‐NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.
Methods:
This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI‐R or PPI‐NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.
Results:
We found several esophageal miRNAs with different expression values between PPI‐R and PPI‐NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI‐R displayed a significant decrease in eotaxin‐3, IL‐5, IL‐13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).
Conclusions:
Esophageal miRNA levels found are able to discriminate between both PPI‐R and PPI‐NR at baseline, and before and after treatment in PPI‐R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI‐R patients after PPI therapy.</description><subject>Biomarkers - analysis</subject><subject>Child</subject><subject>eosinophilic esophagitis</subject><subject>Eosinophilic Esophagitis - drug therapy</subject><subject>Eosinophilic Esophagitis - genetics</subject><subject>esophagus</subject><subject>Humans</subject><subject>Male</subject><subject>microRNA</subject><subject>MicroRNAs - metabolism</subject><subject>Original : Gastroenterology: Eosinophilic GI Disease</subject><subject>Prospective Studies</subject><subject>Proton Pump Inhibitors - therapeutic use</subject><subject>proton‐pump inhibitor</subject><subject>responsiveness</subject><issn>0277-2116</issn><issn>1536-4801</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EokPhDRDKkk2Kr2PHyQKkdjT9QaWMKiqWlid2JgbHDnZC1R2P0GfkSfBoplVhAViyrCt_51z7HoReAj4AXPM3H5YnB_jBIjXjj9AMWFHmtMLwGM0w4TwnAOUeehbjlwRxyvBTtFcUGBdQ0hkalsGP3v38cTtM_ZCduc6szOhDdqnj4F3U2TJoZZrReJddRePW2SL6oZNrLW3Wmyb4y4vDmBmXzTtjVdAu-2zGLlv4BCfQWNPcScxo4nP0pJU26he7cx9dHS8-zU_z848nZ_PD87xhrOS5WimmeKlaSRUvFCOkqrGuKTCgtC01kKZtOMUrkKRSgHUJNQHdMKnaFpdVsY_ebX2HadVr1Wg3BmnFEEwvw43w0ojfb5zpxNp_F5ynZgVJBq93BsF_m3QcRW9io62VTvspCkJpRQFTzBNKt2iaRoxBt_dtAItNWCKFJf4MK8lePXzivegunQRUW-Da21GH-NVO1zqILo1-7P7lTf8i3WAMeJkTTDCQVOVpw6bj253MWH3zX98Q75cXxdExJkBZ8QtNS8VG</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Cañas, José Antonio</creator><creator>Tabares, Ana</creator><creator>Barbero, Claudia</creator><creator>García‐Sánchez, Daniel</creator><creator>Sastre, Beatriz</creator><creator>Rodrigo‐Muñoz, José Manuel</creator><creator>Mahíllo‐Fernández, Ignacio</creator><creator>Rayo, Ana</creator><creator>Borrell, Belén</creator><creator>Cilleruelo, Mª Luz</creator><creator>Román, Enriqueta</creator><creator>Fernandez‐Fernandez, Sonia</creator><creator>Gutiérrez‐Junquera, Carolina</creator><creator>Pozo, Victoria</creator><general>Lippincott Williams & Wilkins</general><general>by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202012</creationdate><title>Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis</title><author>Cañas, José Antonio ; Tabares, Ana ; Barbero, Claudia ; García‐Sánchez, Daniel ; Sastre, Beatriz ; Rodrigo‐Muñoz, José Manuel ; Mahíllo‐Fernández, Ignacio ; Rayo, Ana ; Borrell, Belén ; Cilleruelo, Mª Luz ; Román, Enriqueta ; Fernandez‐Fernandez, Sonia ; Gutiérrez‐Junquera, Carolina ; Pozo, Victoria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5567-dbd5d76dfa4d73d522890e9415144f6e12cfc740b1a28d10e61921ec5adff0683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomarkers - analysis</topic><topic>Child</topic><topic>eosinophilic esophagitis</topic><topic>Eosinophilic Esophagitis - drug therapy</topic><topic>Eosinophilic Esophagitis - genetics</topic><topic>esophagus</topic><topic>Humans</topic><topic>Male</topic><topic>microRNA</topic><topic>MicroRNAs - metabolism</topic><topic>Original : Gastroenterology: Eosinophilic GI Disease</topic><topic>Prospective Studies</topic><topic>Proton Pump Inhibitors - therapeutic use</topic><topic>proton‐pump inhibitor</topic><topic>responsiveness</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cañas, José Antonio</creatorcontrib><creatorcontrib>Tabares, Ana</creatorcontrib><creatorcontrib>Barbero, Claudia</creatorcontrib><creatorcontrib>García‐Sánchez, Daniel</creatorcontrib><creatorcontrib>Sastre, Beatriz</creatorcontrib><creatorcontrib>Rodrigo‐Muñoz, José Manuel</creatorcontrib><creatorcontrib>Mahíllo‐Fernández, Ignacio</creatorcontrib><creatorcontrib>Rayo, Ana</creatorcontrib><creatorcontrib>Borrell, Belén</creatorcontrib><creatorcontrib>Cilleruelo, Mª Luz</creatorcontrib><creatorcontrib>Román, Enriqueta</creatorcontrib><creatorcontrib>Fernandez‐Fernandez, Sonia</creatorcontrib><creatorcontrib>Gutiérrez‐Junquera, Carolina</creatorcontrib><creatorcontrib>Pozo, Victoria</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of pediatric gastroenterology and nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cañas, José Antonio</au><au>Tabares, Ana</au><au>Barbero, Claudia</au><au>García‐Sánchez, Daniel</au><au>Sastre, Beatriz</au><au>Rodrigo‐Muñoz, José Manuel</au><au>Mahíllo‐Fernández, Ignacio</au><au>Rayo, Ana</au><au>Borrell, Belén</au><au>Cilleruelo, Mª Luz</au><au>Román, Enriqueta</au><au>Fernandez‐Fernandez, Sonia</au><au>Gutiérrez‐Junquera, Carolina</au><au>Pozo, Victoria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis</atitle><jtitle>Journal of pediatric gastroenterology and nutrition</jtitle><addtitle>J Pediatr Gastroenterol Nutr</addtitle><date>2020-12</date><risdate>2020</risdate><volume>71</volume><issue>6</issue><spage>755</spage><epage>763</epage><pages>755-763</pages><issn>0277-2116</issn><eissn>1536-4801</eissn><abstract>ABSTRACT
Objectives:
Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton‐pump inhibitors (PPI) induce disease remission but no predictive factors of PPI‐responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI‐R) and nonresponder patients (PPI‐NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy.
Methods:
This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI‐R or PPI‐NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum.
Results:
We found several esophageal miRNAs with different expression values between PPI‐R and PPI‐NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI‐R displayed a significant decrease in eotaxin‐3, IL‐5, IL‐13, periostin, and major basic protein (P < 0.05) and a significant increase in filaggrin levels after PPI treatment (P < 0.01).
Conclusions:
Esophageal miRNA levels found are able to discriminate between both PPI‐R and PPI‐NR at baseline, and before and after treatment in PPI‐R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI‐R patients after PPI therapy.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>33003164</pmid><doi>10.1097/MPG.0000000000002957</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Biomarkers - analysis Child eosinophilic esophagitis Eosinophilic Esophagitis - drug therapy Eosinophilic Esophagitis - genetics esophagus Humans Male microRNA MicroRNAs - metabolism Original : Gastroenterology: Eosinophilic GI Disease Prospective Studies Proton Pump Inhibitors - therapeutic use proton‐pump inhibitor responsiveness |
| title | Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis |
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