Integrative clinical, radiological and molecular analysis for predicting remission and recurrence of Cushing's disease.
Por:
Moreno-Moreno P, Ibáñez-Costa A, Venegas-Moreno E, Fuentes-Fayos AC, Alhambra-Expósito MR, Fajardo-Montañana C, García-Martínez A, Dios E, Vázquez-Borrego MC, Remón-Ruiz P, Cámara R, Lamas C, Padillo-Cuenca JC, Solivera J, Cano DA, Gahete MD, Herrera-Martínez AD, Picó A, Soto-Moreno A, Gálvez-Moreno MÁ, Castaño JP and Luque RM
Publicada:
16 jun 2022
Ahead of Print:
21 mar 2022
Resumen:
INTRODUCTION: ACTH-secreting pituitary tumors (ACTHomas) are associated with severe comorbidities and increased mortality. Current treatments mainly focus in 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: To identify clinical, biochemical, and molecular markers for predicting long-term clinical outcome and remission in ACTHomas. MATHERIALS AND METHODS: A retrospective multicenter study was performed with 60 ACTHomas patients diagnosed between 2004-2018 and with at least two 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 first surgery. RESULTS: Clinical variables including tumor size, time until diagnosis/first surgery, serum prolactin and post-surgery cortisol levels were associated with tumor- remission and relapsed-disease. The molecular markers analyzed were distinctly expressed in ACTHomas, some components (i.e., SSTR1, CRHR1 and MKI67) showing instructive associations with recurrence and/or remission. Notably, an integrative model including selected clinical variables (tumor-size/post-surgery serum cortisol) and molecular markers (SSTR1/CRHR1) can accurately predict the clinical evolution and remission of patients with ACTHomas, generating a ROC curve with an AUC of 1 (p<0.001). CONCLUSIONS: This study provides a relevant clinical conclusion, demonstrating 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 post-surgery molecular profile represents a valuable tool for clinical evaluation and follow-up of patients with ACTHomas.
Filiaciones:
Moreno-Moreno P:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Service of Endocrinology and Nutrition, IMIBIC, HURS, 14004 Cordoba, Spain
Ibáñez-Costa A:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Venegas-Moreno E:
Unidad de Gestión de Endocrinología y Nutrición. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
Fuentes-Fayos AC:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Alhambra-Expósito MR:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Service of Endocrinology and Nutrition, IMIBIC, HURS, 14004 Cordoba, Spain
Fajardo-Montañana C:
Department of Endocrinology, Hospital Universitario de La Ribera, Alzira, 46600, Valencia, Spain
García-Martínez A:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
Dios E:
Unidad de Gestión de Endocrinología y Nutrición. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
Vázquez-Borrego MC:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Remón-Ruiz P:
Unidad de Gestión de Endocrinología y Nutrición. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
Cámara R:
Department of Endocrinology and Nutrition, Polytechnic University Hospital La Fe, 46026, Valencia, Spain
Lamas C:
Department of Endocrinology and Nutrition, Albacete University Hospital, 02006, Albacete, Spain
Padillo-Cuenca JC:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Service of Endocrinology and Nutrition, IMIBIC, HURS, 14004 Cordoba, Spain
Solivera J:
Service of Neurosurgery, HURS, 14004 Cordoba, Spain
Cano DA:
Unidad de Gestión de Endocrinología y Nutrición. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
Gahete MD:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Herrera-Martínez AD:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Service of Endocrinology and Nutrition, IMIBIC, HURS, 14004 Cordoba, Spain
:
Department of Endocrinology and Nutrition, Alicante General University Hospital. Institute for Health and Biomedical Research (ISABIAL). University Miguel Hernandez. CIBER Rare Diseases, 03010, Alicante, Spain
Soto-Moreno A:
Unidad de Gestión de Endocrinología y Nutrición. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain
Gálvez-Moreno MÁ:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Service of Endocrinology and Nutrition, IMIBIC, HURS, 14004 Cordoba, Spain
Castaño JP:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
Luque RM:
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Cordoba, Spain
Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain
Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain
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