Portal de investigación
Molecular profiling for acromegaly treatment: a validation study
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- 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
- Fajardo-Montanana, C
- Alvarez, CV
- Bernabeu, I
- Marazuela, M
- REMAH Investigators
Grupos
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 1351-0088, 1479-6821
- Tipo:
- Article
- Páginas:
- 375-389
- DOI:
- 10.1530/ERC-18-0565
- Factor de Impacto:
- 1,892 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
ENDOCRINE-RELATED CANCER BIOSCIENTIFICA LTD
Citas Recibidas en Web of Science: 26
Documentos
- No hay documentos
Filiaciones
Keywords
- acromegaly; E-cadherin; SSTR2; Ki-67; predictive response; somatostatin receptor ligands (SRL); somatostatin analogues
Proyectos asociados
ESTUDIO FASE III, MULTICENTRICO, ALEATORIZADO, DOBLE CIEGO DE 48 SEMANAS, CON UN PERIDO INICIAL DE 12 SEMANAS CONTROLADO CON PLACEBO, PARA EVALUAR LA SEGURIDAD Y LA EFICACIA DE OSILODROSTAT EN PACIENTES CON ENFERMEDADES DE CUSHING.
Investigador Principal: ROSA CÁMARA GÓMEZ
CLCI699C2302 . 2016
ESTUDIO DE EXTENSIÓN, MULTICÉNTRICO, ABIERTO PARA EVALUAR LA SEGURIDAD A LARGO PLAZO EN PACIENTES CON SÍNDROME DE CUSHING ENDÓGENO QUE HAYAN COMPLETADO UN ESTUDIO ANTERIOR DE OSILODROSTAT (LCI699) PATROCINADO POR NOVARTIS Y QUE EL INVESTIGADOR CONSIDERE QUE SE ESTÁN BENEFICIANDO DEL TRATAMIENTO CONTINUADO CON OSILODROSTAT.
Investigador Principal: ROSA CÁMARA GÓMEZ
CLCI699C2X01B . 2018
ESTUDIO OBSERVACIONAL, TRASVERSAL Y MULTICÉNTRICO PARA VALORAR EL CUMPLIMENTO TERAPÉUTICO CON SOMAVERT® EN PACIENTES CON ACROMEGALIA EN CONDICIONES DE PRÁCTICA CLÍNICA HABITUAL.
Investigador Principal: ROSA CÁMARA GÓMEZ
PFI-PEG-2014-01 . 2015
ESTUDIO MUNDIAL SOBRE EL CONTROL Y LAS COMPLICACIONES DEL HIPOTITUITARISMO (HYPOCCS).
Investigador Principal: JUAN FRANCISCO MERINO TORRES
B9R-MC-GDGA . 2011
Cita
Puig M,Gil J,Sampedro M,Jorda M,Webb SM,Serra G,Pons L,Salinas I,Blanco A,Marques M,Valassi E,Pico A,Garcia A,Carrato C,Buj R,del Pozo C,Obiols G,Villabona C,Camara R,Fajardo C,Alvarez CV,Bernabeu I,Marazuela M,REMAH I. Molecular profiling for acromegaly treatment: a validation study. Endocr Relat Cancer. 2020. 27. (6):p. 375-389. IF:5,678. (1).