Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease
| العنوان: | Integrative Clinical, Radiological, and Molecular Analysis for Predicting Remission and Recurrence of Cushing Disease |
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| المؤلفون: | Paloma Moreno-Moreno, Alejandro Ibáñez-Costa, Eva Venegas-Moreno, Antonio C Fuentes-Fayos, María R Alhambra-Expósito, Carmen Fajardo-Montañana, Araceli García-Martínez, Elena Dios, Mari C Vázquez-Borrego, Pablo Remón-Ruiz, Rosa Cámara, Cristina Lamas, José Carlos Padillo-Cuenca, Juan Solivera, David A Cano, Manuel D Gahete, Aura D Herrera-Martínez, Antonio Picó, Alfonso Soto-Moreno, María Ángeles Gálvez-Moreno, Justo P Castaño, Raúl M Luque |
| المساهمون: | Junta de Andalucía, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Grupo Español de Tumores Neuroendocrinos y Endocrinos, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (España), Herrera-Martínez, Aura D., Castaño, Justo P., Luque, Raúl M. |
| المصدر: | The Journal of Clinical Endocrinology & Metabolism. 107:e2938-e2951 |
| بيانات النشر: | The Endocrine Society, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Hydrocortisone, Remission, Cushing disease, Biochemical variables, Pituitary Diseases, Endocrinology, Diabetes and Metabolism, ACTH-secreting pituitary tumors, Remission Induction, Biochemistry (medical), Clinical Biochemistry, Molecular markers, Relapsed disease, Biochemistry, Treatment Outcome, Endocrinology, Predictive biomarkers, Recurrence, Pituitary Gland, Humans, Pituitary Neoplasms, Pituitary ACTH Hypersecretion, Retrospective Studies |
| الوصف: | [Context] Adrenocorticotropin (ACTH)-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus on remission and prevention of persistent disease and recurrence. However, there are still no useful biomarkers to accurately predict the clinical outcome after surgery, long-term remission, or disease relapse. [Objectives] This work aimed to identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. [Methods] A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004 and 2018 with at least 2 years’ follow-up. Clinical/biochemical variables were evaluated yearly. Molecular expression profile of the somatostatin/ghrelin/dopamine regulatory systems components and of key pituitary factors and proliferation markers were evaluated in tumor samples after the first surgery. [Results] Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin, and postsurgery cortisol levels were associated with tumor remission and relapsed disease. The molecular markers analyzed were distinctly expressed in ACTHomas, with some components (ie, SSTR1, CRHR1, and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor size/postsurgery serum cortisol), and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a receiver operating characteristic curve with an area under the curve of 1 (P [Conclusion] This study demonstrates that the combination of a set of clinical and molecular biomarkers in ACTHomas is able to accurately predict the clinical evolution and remission of patients. Consequently, the postsurgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas. This work was supported by the Junta de Andalucía (Nos. P20_00442, PEER-0048-2020, A-0006-2017, A-0055-2018, C-0015-2014, RC-0006-2018; postdoctoral grant DOC_01584, and BIO-0139); Ministry of Science and Innovation (Nos. PID2019-105564RB-I00 and PID2019-105201RB-I00); Instituto de Salud Carlos III, cofunded by the European Union (ERDF/ESF, “Investing in your future”; Nos. PI13/02043; PI16/00175, PI21/01012, and Sara Borrell programme CD19/00255); Spanish Ministry of Universities (predoctoral contract FPU16-05059); a GETNE2019 research grant; and CIBERobn. CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain. |
| تدمد: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgac172 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a1980fe127836811817d4895ecbc338 https://doi.org/10.1210/clinem/dgac172 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3a1980fe127836811817d4895ecbc338 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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| DOI: | 10.1210/clinem/dgac172 |