The Search of miRNA Related to Invasive Growth of Nonfunctioning Gonadotropic Pituitary Tumors.

Joanna Boresowicz,Mateusz Bujko,Paulina Kober,Natalia Rusetska,Maria Maksymowicz,Agnieszka Paziewska,Jacek Kunicki,Janusz A Siedlecki,Michalina Dąbrowska,Wiesław Bonicki,Jerzy Ostrowski,Natalia Zeber-Lubecka

doi:10.1155/2020/3730657

Abstract

Purpose Nonfunctioning gonadotropic pituitary neuroendocrine tumors (PitNETs) are among the most frequent neoplasms of pituitary gland. Although PitNETs are commonly considered benign, a notable part of patients suffer from tumor recurrence after treatment. Invasive growth of pituitary tumor is among the most important prognostic factors. Since molecular features of invasiveness are of potential clinical usefulness, this study was aimed to verify whether invasive and noninvasive nonfunctioning gonadotropic PitNETs differ in the miRNA expression profile and whether the differences could provide a possible molecular classifier. Methods miRNA profiles were determined in 20 patients (11 invasive and 9 noninvasive tumors) using next-generation sequencing. The expression of selected miRNAs was assessed in the independent cohort of 80 patients with qRT-PCR. Results When miRNA profiles of invasive and noninvasive tumors were compared, 29 miRNAs were found differentially expressed. Hsa-miR-184, hsa-miR-181a-2-3p, hsa-miR-93-3p, hsa-miR-574-5p, hsa-miR-185-5p, and hsa-miR-3200-5p showed a potential clinical value according to ROC curve analysis. Unfortunately, differential expression of only hsa-miR-185-5p was confirmed in the validation cohort, with AUG at 0.654. Conclusion Differences in miRNAs expression profiles in invasive and noninvasive gonadotropic PitNETs are slight and the level of miRNA expression seems not to be applicable as useful classifier of tumor invasiveness.

Highlights

Pituitary neuroendocrine tumors (PitNETs) are the third most common intracranial neoplasms in adults, accounting for approximately 16.5% of all tumors in this location [1].ey are classified into subtypes originating from the particular functional type of pituitary cells and are characterized by overproduction of specific hormones [2]
Nonfunctioning PitNETs are considered benign neoplasms; a large proportion of them are characterized by the invasive growth that is manifested by infiltration of adjacent structures by the tumor
Cavernous sinus invasion was defined by extension of adenoma beyond the line corresponding to the lateral tangents of the intracavernous carotid artery (Grades 3 and 4) as defined by Micko et al [18, 19]

Summary

Introduction

Pituitary neuroendocrine tumors (PitNETs) are the third most common intracranial neoplasms in adults, accounting for approximately 16.5% of all tumors in this location [1].ey are classified into subtypes originating from the particular functional type of pituitary cells and are characterized by overproduction of specific hormones [2]. 33% of PitNETs are clinically nonfunctioning tumors, which do not cause any specific endocrinological symptoms and the bulk of nonfunctioning PitNETs are those derived from gonadotroph pituitary cells [3]. International Journal of Endocrinology growth has important clinical implications because it hampers complete tumor resection, which is a basic treatment of nonfunctioning gonadotroph tumors and results in tumor recurrence [2,3,4]. It is one of the most important prognostic features for patients suffering from PitNETs [4]. MicroRNAs (miRNAs) are small noncoding RNA particles that play a pivotal role in posttranscriptional gene silencing. It became clear that they play a role in pathogenesis of pituitary tumors as well [8, 9]

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