Pituitary and neuroendocrinology
Ricardo Blázquez-Encinas 1,2,3,4 , María T. Caro 1,2,5 , Víctor García-Vioque 1,2,3,4 , Sergio Pedraza-Arévalo 1,2,3,4 , Emilia Alors-Pérez 1,2,3,4 , M. Trinidad Moreno-Montilla 1,2,3,4 , Aura D. Herrera-Martínez 1,2,6 , Rafael Sánchez-Sánchez 1,2,5 , A. Salvatierra 1,2,7 , Raquel Serrano-Blanch 1,2,8 , Manuel D. Gahete 1,2,3,4 , Matthieu Foll 9 , Raúl M Luque 1,2,3,4 , Lynnette Fernandez-Cuesta 9 , Alejandro Ibáñez Costa 1,2,3,4 & Justo P. Castaño 1,2,3,4,
1Maimonides Biomedical Research Institute of Cordoba, Cordoba, Spain; 2Reina Sofia University Hospital, Cordoba, Spain; 3Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition, Cordoba, Spain; 5Service of Pathology; 6Service of Endocrinology and Nutrition; 7Service of Thoracic Surgery; 8Service of Medical Oncology; 9International Agency for Research on Cancer, Lyon, France
Introduction: Emerging evidence indicates that dysregulation of alternative splicing represents a new hallmark of cancer. This dysregulation may arise from mutations or altered expression of specific components of the splicing machinery. To date, splicing machinery status has not been studied in lung neuroendocrine neoplasms: typical and atypical pulmonary carcinoids.
Objectives: Here, we aimed to analyzing the splicing machinery in pulmonary carcinoids and exploring its relationship with alternative splicing pattern.
Methods: A custom-made qPCR array was used to measure the expression of the main components of the splicing machinery in a cohort of 33 pulmonary carcinoids patients (tumor vs. adjacent tissue). Results were validated using a publicly available external cohort of 51 patients. Statistical analyses were made to study its association with clinical parameters of the patients. In addition, alternative splicing analyses were performed in RNAseq data of a cohort of 20 patients using SUPPA2 tool.
Results: One third of the components of the splicing machinery were dysregulated in pulmonary carcinoids. Remarkably, a discrete subset of specific components of the spliceosome, as well as key splicing factors displayed significant associations to key clinical parameters, including tumor stage and tumor dissemination. These results were validated in the external cohort of patients, and key components were selected based on their relevance and the association to clinical parameters. Alternative splicing analyses in RNAseq data showed that the expression of these key components was correlated to altered patterns of alternative splicing.
Conclusions: Our results indicate that the splicing machinery is severely dysregulated in pulmonary carcinoids, where some of its components are associated to key clinical parameters of tumor malignancy. These results unveil new avenues to study pulmonary carcinoids and discover new diagnostic/prognostic and therapeutic tools.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more