Background: Non-functioning pituitary adenomas (NFPAs) necessitate prolonged clinical, biochemical and radiological observation, constituting a significant burden in terms of medical resources and societal costs. Reliable biomarkers associated with aggressiveness and recurrence of NFPAs are lacking. As the growth of tumor remnants is highly variable, molecular markers that can predict growth potential and tumor behavior are necessary.
Aim: To identify target genes in fast- and slow- growing NFPAs estimated by postoperative initial tumor volume doubling time (TVDT), and to find reliable biomarkers predicting the growth potential of the remnant tumor, focusing on the specific role of epithelial-mesenchymal transition (EMT) process.
Material and methods: RNA sequencing was performed in gonadotroph NFPAs with short TVDT (median <30.05 months, fast group, n=4) and long TVDT (median >30.05 months, slow group, n=4). Data was analyzed by tophat2 and cufflinks/cummeRbund pipeline. Furthermore, genes (n=40) were selected based on significance, fold of change and pathway analysis for validation with RT-qPCR in a larger cohort of gonadotroph NFPAs (n=20, 13 male).
Results: RNA sequencing identified 350 genes significantly differentially expressed, between the two groups (285 genes up- and 65 down- regulated in the fast group, P adjusted <0.05). Of the 40 genes chosen for further validation by RT-qPCR, 11 showed significant correlations with TVDT (−0.669≤R≥−0.466, P<0.05). These were six genes involved in EMT (PCDH18, SPAG9, SKIL, MTDH, HOOK1 and CNOT6L), and also UNC5D, EMCN, MYO1B, GPM6A and PRKACB.
Conclusions: Fast- and slow- growing NFPAs show different gene expression profiles. Genes known as related to EMT have higher expression in fast-growing tumors, suggesting a pathogenic role in tumor growth. The identified genes and their products could represent useful markers for predicting tumor aggressiveness and recurrence, and may be potential targets for drug therapy.
20 - 23 May 2017
European Society of Endocrinology