ECE2015 Guided Posters Pituitary–Basic and IGF-1 (9 abstracts)
Role of miR-375 in oncogenesis of pituitary adenomas
Laura Sanchez-Tejada 5 , Ruth Sanchez-Ortiga 1 , Pedro Riesgo 8 , Javier Abarca 6 , Carmen Fajardo 3 , Irene Monjas 7 , Rosa Cámara 4 , Cristina Lamas 2 & Antonio Picó 1
1Endocrinology Department, Hospital General Universitario Alicante, Alicante, Spain; 2Endocrinology Department, Hospital General Universitario Albacete, Albacete, Spain; 3Endocrinology Department, Hospital La Ribera, Alzira, Spain; 4Endocrinology Department, Hospital Universitario La Fe, Valencia, Spain; 5Research Unit, Hospital General Universitario Alicante, Alicante, Spain; 6Neurosurgery Department, Hospital General Universitario Alicante, Alicante, Spain; 7Otorhinolaryngology Department, Hospital General Universitario Alicante, Alicante, Spain; 8Neurosurgery Department, Hospital La Ribera, Alzira, Spain.
Purpose: MicroRNAs (miRNAs) are a fundamental component of gene regulation mechanisms. Presently, altered miRNA patterns of expression have been documented in different human cancers, and they may explain the distinct behavior of pituitary adenomas (PA) and the differences between subtypes. miR-375 can target among other genes to IGF1 receptor (IGF1R) and participes in reprogramming cancer cell metabolism. The aim of this study was to assess the miR-375 role on pathogenesis of different PA subtypes.
Methods: In this cross-sectional descriptive study, we evaluated miR-375 by qRT-PCR analysis on 60 human PA samples: 29 gonadotrophs (GT), 15 somatotrophs (ST), eight functioning corticotroph (CT), and eight silent corticotroph adenomas (SCA). Nine healthy pituitary from autopsies were used as calibrator reference. Aggressiveness was graded according to invasiveness (Hardy’s grade IV) and Ki-67 gene expression (>2.59 fold change (FC)).
Results: In our whole sample miR-375 was associated with sex (men: 3.00 (1.63–4.36) FC values vs women: 1.35 (0.47–1.92) FC values, P=0.002) and was positively correlated with age (r=0.466, P=0.000). miR-375 expression patterns differed depending on PA subtype (P=0.000) and non functioning PA (GT and SCA) revealed overexpression compared with functioning PA (CT and ST) (81.3 (26/37) vs 39.3 (11/23)), entailed a risk of 6.7 (2.1–21.5) times higher (P=0.001). Its expression was also correlated with tumor maximum diameter (r=0.303, P=0.022) and associated with their extension (intrasellar: 1.05 (0.47–1.47); extrasellar: 2.50 (1.47–4.39); and invasive: 2.50 (1.07–3.88); P=0.008). In addition, 66.7% tumors with high or medium aggressiveness grades overexpressed miR-375 vs 28.6% with low grade, which entailed a risk 5.0 (1.6–16.0) times higher (P=0.005).
Conclusion: Our results revealed a different role for miR-375 in the pathogenesis of PA depending on subtype. This miRNA may be a marker of aggressiveness, but further studies are needed for endorse this utility.
Disclosure: This work was supported by FISABIO (FCVI-HGUA-2012-C01).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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