Endocrine Abstracts

Pituitary neuroendocrine tumors (PitNETs) are non-metastatic neoplasms of the pituitary that may overproduce hormones leading to systemic disorders or tumor mass effects causing headache, vertigo, or visual impairment. The overall estimated clinical prevalence of PitNETs is 1 in 400 to 1 in 1000 people. Although the pathogenesis of PitNETs has been extensively studied the molecular factors underlying tumorigenesis, remission, and therapy response of PitNETs are still unclear. The studies of PitNET transcriptome profiles could give insight into pathogenesis mechanisms that promote tumorigenesis properties like growth, invasiveness, response to treatment. First-line medical treatment of somatotroph PitNETs is somatostatin analogues (SSA) and dopamine agonists (DA) that decrease tumour mass and induce antiproliferative effects on PitNET cells. This study aimed to determine differences in transcriptome signatures that are induced by SSA/DA therapy in PitNET tissue. In this study we selected tumour tissue of twelve patients with somatotroph PitNETs, half of the patients had SSA/DA treatment before surgery and the other half was treatment-naive. The transcriptome sequencing was carried out, differentially expressed genes (DEGs) were identified and protein–protein interactions and pathway analysis was performed. We discovered 34 upregulated and 6 downregulated DEGs in patients with SSA/DA treatment. Three tumour development promoting factors MUC16, MACC1 and GRHL2 were significantly downregulated in therapy administered PitNET tissue. Protein–protein interactions and pathway analysis revealed extracellular matrix Here, we demonstrate that somatotroph PitNETs can be distinguished based on their transcriptional profiles following SSA/DA therapy, therefore, SSA/DA treatment can cause changes in gene expression. The SSA/DA significantly downregulated several tumourigenesis contributing factors, including MUC16, MACC1 and GRHL2. Genes that were upregulated did not have a direct influence on the antiproliferative functions in the PitNET cells. This suggests that SSA acts in a tumour suppressive manner. Collagen related interactions and pathways were enriched in our data implicating extracellular matrix involvement in antitumoural effects of drug treatment.