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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Authors: Puig-Domingo, M, Gil, J, Sampedro-Nunez, M, Jorda, M, Webb, SM, Serra, G, Pons, L, Salinas, I, Blanco, A, Marques-Pamies, M, Valassi, E, Pico, A, Garcia-Martinez, A, Carrato, C, Buj, R, del Pozo, C, Obiols, G, Villabona, C, Camara, R, Fajardo-Montanana, C, Alvarez, CV, Bernabeu, I, Marazuela, M, REMAH Investigators
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repository:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p6737
Online Access:https://isabial.portalinvestigacion.com/publicaciones6737
Access Level:Open access
Keyword:acromegaly
E-cadherin
SSTR2
Ki-67
predictive response
somatostatin receptor ligands (SRL)
somatostatin analogues
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spelling Molecular profiling for acromegaly treatment: a validation studyPuig-Domingo, MGil, JSampedro-Nunez, MJorda, MWebb, SMSerra, GPons, LSalinas, IBlanco, AMarques-Pamies, MValassi, EPico, AGarcia-Martinez, ACarrato, CBuj, Rdel Pozo, CObiols, GVillabona, CCamara, RFajardo-Montanana, CAlvarez, CVBernabeu, IMarazuela, MREMAH InvestigatorsacromegalyE-cadherinSSTR2Ki-67predictive responsesomatostatin receptor ligands (SRL)somatostatin analoguesPharmacologic 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.BIOSCIENTIFICA LTD2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones6737ENDOCRINE-RELATED CANCERISSN: 13510088ISSNe: 14796821reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p67372026-06-12T10:20:37Z
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, M
acromegaly
E-cadherin
SSTR2
Ki-67
predictive response
somatostatin receptor ligands (SRL)
somatostatin analogues
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, M
Gil, J
Sampedro-Nunez, M
Jorda, M
Webb, SM
Serra, G
Pons, L
Salinas, I
Blanco, A
Marques-Pamies, M
Valassi, E
Pico, A
Garcia-Martinez, A
Carrato, C
Buj, R
del Pozo, C
Obiols, G
Villabona, C
Camara, R
Fajardo-Montanana, C
Alvarez, CV
Bernabeu, I
Marazuela, M
REMAH Investigators
author Puig-Domingo, M
author_facet Puig-Domingo, M
Gil, J
Sampedro-Nunez, M
Jorda, M
Webb, SM
Serra, G
Pons, L
Salinas, I
Blanco, A
Marques-Pamies, M
Valassi, E
Pico, A
Garcia-Martinez, A
Carrato, C
Buj, R
del Pozo, C
Obiols, G
Villabona, C
Camara, R
Fajardo-Montanana, C
Alvarez, CV
Bernabeu, I
Marazuela, M
REMAH Investigators
author_role author
author2 Gil, J
Sampedro-Nunez, M
Jorda, M
Webb, SM
Serra, G
Pons, L
Salinas, I
Blanco, A
Marques-Pamies, M
Valassi, E
Pico, A
Garcia-Martinez, A
Carrato, C
Buj, R
del Pozo, C
Obiols, G
Villabona, C
Camara, R
Fajardo-Montanana, C
Alvarez, CV
Bernabeu, I
Marazuela, M
REMAH Investigators
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv acromegaly
E-cadherin
SSTR2
Ki-67
predictive response
somatostatin receptor ligands (SRL)
somatostatin analogues
topic acromegaly
E-cadherin
SSTR2
Ki-67
predictive response
somatostatin receptor ligands (SRL)
somatostatin analogues
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones6737
url https://isabial.portalinvestigacion.com/publicaciones6737
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BIOSCIENTIFICA LTD
publisher.none.fl_str_mv BIOSCIENTIFICA LTD
dc.source.none.fl_str_mv ENDOCRINE-RELATED CANCER
ISSN: 13510088
ISSNe: 14796821
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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