Molecular profiling for acromegaly treatment: a validation study

Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of diff...

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Autores: Puig-Domingo, Manel, Gil, Joan, Sampedro-Nuñez, Miguel, Jordà, Mireia, Webb, Susan M., Serra, Guillermo, Pons, Laura, Salinas, Isabel, Blanco, Alberto, Marques-Pamies, Montserrat, Valassi, Elena, Picó, Antonio, García-Martínez, Araceli, Carrato, Cristina, Buj, Raquel, del Pozo, Carlos, Obiols, Gabriel, Villabona, Carles, Cámara, Rosa, Fajardo Montañana, Carmen, Alvarez, Clara V., Bernabéu, Ignacio, Marazuela, Mónica
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/7506
Acceso en línea:https://hdl.handle.net/20.500.12466/7506
Access Level:acceso abierto
Palabra clave:Acromegaly
E-cadherin
SSTR2
Ki-67
Predictive response
Somatostatin receptor ligands (SRL)
Somatostatin analogues
32 Ciencias Médicas
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spelling Molecular profiling for acromegaly treatment: a validation studyPuig-Domingo, ManelGil, JoanSampedro-Nuñez, MiguelJordà, MireiaWebb, Susan M.Serra, GuillermoPons, LauraSalinas, IsabelBlanco, AlbertoMarques-Pamies, MontserratValassi, ElenaPicó, AntonioGarcía-Martínez, AraceliCarrato, CristinaBuj, Raqueldel Pozo, CarlosObiols, GabrielVillabona, CarlesCámara, RosaFajardo Montañana, CarmenAlvarez, Clara V.Bernabéu, IgnacioMarazuela, MónicaAcromegalyE-cadherinSSTR2Ki-67Predictive responseSomatostatin receptor ligands (SRL)Somatostatin analogues32 Ciencias MédicasPharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.20262026-02-1320202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12466/7506reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/75062026-06-19T08:32:07Z
dc.title.none.fl_str_mv Molecular profiling for acromegaly treatment: a validation study
title Molecular profiling for acromegaly treatment: a validation study
spellingShingle Molecular profiling for acromegaly treatment: a validation study
Puig-Domingo, Manel
Acromegaly
E-cadherin
SSTR2
Ki-67
Predictive response
Somatostatin receptor ligands (SRL)
Somatostatin analogues
32 Ciencias Médicas
title_short Molecular profiling for acromegaly treatment: a validation study
title_full Molecular profiling for acromegaly treatment: a validation study
title_fullStr Molecular profiling for acromegaly treatment: a validation study
title_full_unstemmed Molecular profiling for acromegaly treatment: a validation study
title_sort Molecular profiling for acromegaly treatment: a validation study
dc.creator.none.fl_str_mv Puig-Domingo, Manel
Gil, Joan
Sampedro-Nuñez, Miguel
Jordà, Mireia
Webb, Susan M.
Serra, Guillermo
Pons, Laura
Salinas, Isabel
Blanco, Alberto
Marques-Pamies, Montserrat
Valassi, Elena
Picó, Antonio
García-Martínez, Araceli
Carrato, Cristina
Buj, Raquel
del Pozo, Carlos
Obiols, Gabriel
Villabona, Carles
Cámara, Rosa
Fajardo Montañana, Carmen
Alvarez, Clara V.
Bernabéu, Ignacio
Marazuela, Mónica
author Puig-Domingo, Manel
author_facet Puig-Domingo, Manel
Gil, Joan
Sampedro-Nuñez, Miguel
Jordà, Mireia
Webb, Susan M.
Serra, Guillermo
Pons, Laura
Salinas, Isabel
Blanco, Alberto
Marques-Pamies, Montserrat
Valassi, Elena
Picó, Antonio
García-Martínez, Araceli
Carrato, Cristina
Buj, Raquel
del Pozo, Carlos
Obiols, Gabriel
Villabona, Carles
Cámara, Rosa
Fajardo Montañana, Carmen
Alvarez, Clara V.
Bernabéu, Ignacio
Marazuela, Mónica
author_role author
author2 Gil, Joan
Sampedro-Nuñez, Miguel
Jordà, Mireia
Webb, Susan M.
Serra, Guillermo
Pons, Laura
Salinas, Isabel
Blanco, Alberto
Marques-Pamies, Montserrat
Valassi, Elena
Picó, Antonio
García-Martínez, Araceli
Carrato, Cristina
Buj, Raquel
del Pozo, Carlos
Obiols, Gabriel
Villabona, Carles
Cámara, Rosa
Fajardo Montañana, Carmen
Alvarez, Clara V.
Bernabéu, Ignacio
Marazuela, Mónica
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Acromegaly
E-cadherin
SSTR2
Ki-67
Predictive response
Somatostatin receptor ligands (SRL)
Somatostatin analogues
32 Ciencias Médicas
topic Acromegaly
E-cadherin
SSTR2
Ki-67
Predictive response
Somatostatin receptor ligands (SRL)
Somatostatin analogues
32 Ciencias Médicas
description Pharmacologic treatment of acromegaly is currently based upon assay-error strategy, the first-generation somatostatin receptor ligands (SRL) being the first-line treatment. However, about 50% of patients do not respond adequately to SRL. Our objective was to evaluate the potential usefulness of different molecular markers as predictors of response to SRL. We used somatotropinoma tissue obtained after surgery from a national cohort of 100 acromegalic patients. Seventy-one patients were treated with SRL during at least 6 months under maximal therapeutic doses according to IGF1 values. We analyzed the expression of SSTR2, SSTR5, AIP, CDH1 (E-cadherin), MKI67 (Ki-67), KLK10, DRD2, ARRB1, GHRL, In1-Ghrelin, PLAGL1 and PEBP1 (RKIP) by RT-qPCR and mutations in GNAS gene by Sanger sequencing. The response to SRL was categorized as complete response (CR), partial (PR) or non-response (NR) if IGF1 was normal, between >2<3 SDS or >3 SDS IGF1 at 6 months of follow-up, respectively. From the 71 patients treated, there were 27 CR (38%), 18 PR (25%) and 26 NR (37%). SSTR2, Ki-67 and E-cadherin were associated with SRL response (P < 0.03, P < 0.01 and P < 0.003, respectively). E-cadherin was the best discriminator for response prediction (AUC = 0.74, P < 0.02, PPV of 83.7%, NPV of 72.6%), which was validated at protein level. SSTR5 expression was higher in patients pre-treated with SRL before surgery. We conclude that somatotropinomas showed heterogeneity in the expression of genes associated with SRL response. E-cadherin was the best molecular predictor of response to SRL. Thus, the inclusion of E-cadherin in subsequent treatment-decision after surgical failure may be useful in acromegaly.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01
2020
2020-01-01
2026
2026-02-13
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12466/7506
url https://hdl.handle.net/20.500.12466/7506
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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