Molecular alterations in non-functioning pituitary adenomas

Article type: Research Article

Authors: Taniguchi-Ponciano, Keiko^{a; d} | Gomez-Apo, Erick^b | Chavez-Macias, Laura^{b; c} | Vargas, Guadalupe^{d; e} | Espinosa-Cardenas, Etual^{d; e} | Ramirez-Renteria, Claudia^d | Ferreira-Hermosillo, Aldo^d | Sosa, Ernesto^{d; e} | Silva-Román, Gloria^d | Peña-Martínez, Eduardo^d | Andonegui-Elguera, Sergio^{d; f} | Vargas-Chavez, Sonia^a | Santiago-Andres, Yorgui^a | Peralta, Raul^g | Marrero-Rodríguez, Daniel^{d; *} | Mercado, Moises^{d; *}

Affiliations: [a] Laboratorio de Neuroendocrinología Comparada, Departamento de Ecología y Recursos Naturales, Biología, Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico | [b] Área de Neuropatología, Servicio de Anatomía Patológica, Hospital General de México Dr. Eduardo Liceaga, Mexico City, Mexico | [c] Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico | [d] Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico | [e] Servicio de Endocrinologia, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico | [f] Departamento de Desarrollo Tecnologico, Instituto Nacional de Medicina Genomica, Mexico City, Mexico | [g] Centro de Investigacion en Dinamica Celular, Universidad Autonoma del Estado de Morelos, Cuernavaca, Mexico

Correspondence: [*] Corresponding authors: Daniel Marrero-Rodríguez and Moisés Mercado, CONACyT-Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, 06720, Mexico. Tel.: +52 5440 1021; E-mails: dan.mar57@gmail.com or mmercadoa@yahoo.com and moises.mercado@endocrinologia.org.mx.

Abstract: BACKGROUND: Clinically non-functioning Pituitary Adenomas (NFPA) are among the most common neoplasms of the sellar region. They usually present with compressive symptoms such as headache and visual field defects and not infrequently, are found incidentally. NFPA are classified as gonadotropinomas, null cell adenomas, according to their immunohistochemical phenotype. The molecular alterations responsible for the development of these lesions are incompletely understood, and there is scarce information regarding the molecular alterations and markers. OBJECTIVE: We carried out an in-silico analysis aimed at identifying the molecular alterations in NFPA and to discover new molecular markers. METHODS: Twenty-three microarray libraries were analyzed. Fourteen correspond to NFPA and 9 to control tissue gland. They were analyzed using Partek Genomic Suite to identify differentially expressed genes and WebGestalt and Metascape to understand the meaning behind the gene lists. RESULTS: Pituitary adenomas showed a markedly different transcriptome compared to the non-tumoral gland, regardless of their putative immunophenotype. Genes related to calcium metabolism such as CACNA2D4, immune-related CXCR4, and stem cell-related KLF8 and PITX2 were altered. CONCLUSIONS: Differentially expressed calcium metabolism and immune-related genes in NFPA represent attractive molecular markers and potential therapeutic targets.

Keywords: Non-functioning pituitary adenomas, null cell, gonadotropinomas, molecular markers

DOI: 10.3233/CBM-191121

Journal: Cancer Biomarkers, vol. 28, no. 2, pp. 193-199, 2020