Aura D Herrera-Martínez1, Manuel D Gahete2, Rafael Sánchez-Sánchez3, Rosa Ortega Salas3, Raquel Serrano-Blanch4, Ángel Salvatierra5, Leo J Hofland6, Raúl M Luque7, María A Gálvez-Moreno8, Justo P Castaño9. 1. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Endocrinology and Nutrition Service, Reina Sofia University Hospital, Córdoba, Spain. 2. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain. 3. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Pathology Service, Reina Sofia University Hospital, Córdoba, Spain. 4. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Medical Oncology Service, Reina Sofia University Hospital, Córdoba, Spain. 5. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Thoracic Surgery and Lung Transplantation Unit, Reina Sofia University Hospital, Córdoba, Spain. 6. Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands. 7. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain. Electronic address: raul.luque@uco.es. 8. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Endocrinology and Nutrition Service, Reina Sofia University Hospital, Córdoba, Spain. Electronic address: mariaa.galvez.sspa@juntadeandalucia.es. 9. Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain. Electronic address: justo@uco.es.
Abstract
BACKGROUND: Lung carcinoids (LCs) are rare tumors that comprise 1-5% of lung malignancies but represent 20-30% of neuroendocrine tumors. Their incidence is progressively increasing and a better characterization of these tumors is required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of various endocrine-related cancers, wherein they may become useful diagnostic, prognostic and therapeutic biomarkers. OBJECTIVES: We aimed to evaluate the expression levels of ghrelin and SST/CORT system components in LCs, as well as to explore their putative relationship with histological/clinical characteristics. PATIENTS AND METHODS: An observational retrospective study was performed; 75 LC patients with clinical/histological characteristics were included. Samples from 46 patients were processed to isolate mRNA from tumor and adjacent non-tumor region, and the expression levels of SST/CORT and ghrelin systems components, determined by quantitative-PCR, were compared to those of 7 normal lung tissues. RESULTS: Patient cohort was characterized by mean age 53±15 years, 48% males, 34% with tobacco exposure; 71.4/28.6% typical/atypical carcinoids, 21.7% incidental tumors, 4.3% functioning tumors, 17.7% with metastasis. SST/CORT and ghrelin system components were expressed at variable levels in a high proportion of tumors, as well as in adjacent non-tumor tissues, while a lower proportion of normal lung samples also expressed these molecules. A gradation was observed from normal non-neoplastic lung tissues, non-tumor adjacent tissue and LCs, being SST, sst4, sst5, GHS-R1a and GHS-R1b overexpressed in tumor tissue compared to normal tissue. Importantly, several SST/CORT and ghrelin system components displayed significant correlations with relevant clinical parameters, such as necrosis, peritumoral and vascular invasion, or metastasis. CONCLUSION: Altogether, these data reveal a prominent, widespread expression of key SST/CORT/ghrelin system components in LCs, where they display clinical-histological correlations, which could provide novel, valuable markers for NET patient management.
BACKGROUND: Lung carcinoids (LCs) are rare tumors that comprise 1-5% of lung malignancies but represent 20-30% of neuroendocrine tumors. Their incidence is progressively increasing and a better characterization of these tumors is required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of various endocrine-related cancers, wherein they may become useful diagnostic, prognostic and therapeutic biomarkers. OBJECTIVES: We aimed to evaluate the expression levels of ghrelin and SST/CORT system components in LCs, as well as to explore their putative relationship with histological/clinical characteristics. PATIENTS AND METHODS: An observational retrospective study was performed; 75 LC patients with clinical/histological characteristics were included. Samples from 46 patients were processed to isolate mRNA from tumor and adjacent non-tumor region, and the expression levels of SST/CORT and ghrelin systems components, determined by quantitative-PCR, were compared to those of 7 normal lung tissues. RESULTS:Patient cohort was characterized by mean age 53±15 years, 48% males, 34% with tobacco exposure; 71.4/28.6% typical/atypical carcinoids, 21.7% incidental tumors, 4.3% functioning tumors, 17.7% with metastasis. SST/CORT and ghrelin system components were expressed at variable levels in a high proportion of tumors, as well as in adjacent non-tumor tissues, while a lower proportion of normal lung samples also expressed these molecules. A gradation was observed from normal non-neoplastic lung tissues, non-tumor adjacent tissue and LCs, being SST, sst4, sst5, GHS-R1a and GHS-R1b overexpressed in tumor tissue compared to normal tissue. Importantly, several SST/CORT and ghrelin system components displayed significant correlations with relevant clinical parameters, such as necrosis, peritumoral and vascular invasion, or metastasis. CONCLUSION: Altogether, these data reveal a prominent, widespread expression of key SST/CORT/ghrelin system components in LCs, where they display clinical-histological correlations, which could provide novel, valuable markers for NET patient management.
Authors: Aura D Herrera-Martínez; Manuel D Gahete; Sergio Pedraza-Arevalo; Rafael Sánchez-Sánchez; Rosa Ortega-Salas; Raquel Serrano-Blanch; Raúl M Luque; María A Gálvez-Moreno; Justo P Castaño Journal: Endocrine Date: 2017-12-01 Impact factor: 3.633
Authors: Yiraldine Herrera-Martínez; Carlos Alzas Teomiro; Soraya León Idougourram; María José Molina Puertas; Alfonso Calañas Continente; Raquel Serrano Blanch; Justo P Castaño; María Ángeles Gálvez Moreno; Manuel D Gahete; Raúl M Luque; Aura D Herrera-Martínez Journal: Cancers (Basel) Date: 2021-12-27 Impact factor: 6.639
Authors: Aura D Herrera-Martínez; Manuel D Gahete; Rafael Sánchez-Sánchez; Emilia Alors-Perez; Sergio Pedraza-Arevalo; Raquel Serrano-Blanch; Antonio J Martínez-Fuentes; Maria A Gálvez-Moreno; Justo P Castaño; Raúl M Luque Journal: Clin Transl Gastroenterol Date: 2018-10-08 Impact factor: 4.488