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

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.

The Involvement of miRNAs in Pituitary Adenomas Pathogenesis and the Clinical Implications

“…In the field of PA research, several reports have confirmed that the abnormal expression of multiple miRNAs is associated with the occurrence and progress of PA [11]. For example, recent studies found that the 14q32 cluster-encoded miRNAs were downregulated in PA [13]; differential expression of hsa-miR-185-5p was confirmed in the validation cohort between invasive and noninvasive gonadotropin secreting PA [14]; miRNA-7a2 regulates prolactin production in ACTH-PA cells [15]. Therefore, miRNAs may play an important role in the pathogenesis of PA and may be used as molecular biomarkers for the early diagnosis of PA and can also provide new ideas for the treatment of PA.…”

MicroRNAs as Potential Biomarkers in Pituitary Adenomas

“…Boresowicz et al [ 40 ] investigated whether a miRNA signature could discriminate NFPA patients with invasive and noninvasive gonadotropic pituitary neuroendocrine tumors (PitNETs), one of the most frequent histopathological subtypes of NFPAs. Comparing miRNome by using next generation sequencing (NGS) and by applying receiver operating characteristics (ROC) curve analysis for the 29 identified differentially expressed miRNAs, the authors found six miRNAs (miR-184, miR-181a-2-3p, miR-93-3p, miR-574-5p, miR-185-5p, and miR-3200-5p) that could be potential biomarkers of invasiveness.…”