Analysis of Potential RNA Biomarkers Expression in Corticotroph Pituitary Neuroendocrine Tumours

Background/Objectives: In recent years, research has highlighted the heterogeneity of corticotroph pituitary neuroendocrine tumors (CPitNETs), which are linked to Cushing’s disease. Purpose of the study is to determine stable postgenomic markers depending on maximum diameter on MRI (without visualization of the pituitary tumor on MRI/less than 6 mm (group 1a) and with visualization on MRI/more than 6 mm (group 1b). Methods: Immunohistochemically determined granulation pattern (group 2a densely granulated, 2b Crooke cell tumor) and proliferation levels based on Ki-67 with a threshold of 3% (group 3a high proliferation, 3b low proliferation), and biological behavior (group 4a indolent, 4b aggressive). Our study analyzed fresh tissue samples of CPitNETs from 34 patients with Cushing’s disease. Total RNA was extracted and sequenced using Cap Analysis Gene Expression (CAGE) on the Illumina HiSeq2500 platform, followed by bioinformatics analysis. Results: Differentially expressed genes were identified in group 1a tumors (EN1, EFS,) versus group1b (LCN1, BMP3). An inverse relationship was found between tumor volume and the expression of the RBM24 and ADGRD2 genes. A direct relationship was found between tumor volume and the expression of the PFN2 and CNTNAP5 genes. Identical gene signatures were found both in densely granulated and Crooke cell variants. Samples from group 3a, 4b and with bigger volume presented upregulated CT45A3, CT45A, CT45A1 genes. Samples from group 3b were enriched with PI3K/Akt pathway. Samples from group 4a showed expression of FXYD3, FGFR3 and FZD9 genes. Conclusions: Identified postgenomic markers in the studied subgroups of CPitNETs can potentially become biomarkers and allow to predict big volume and type of biological behavior at the early stages of diagnosis and treatment of patients with Cushing's disease.