Transcriptome analysis and microRNAs in adrenal tumours
The analysis of mRNA expression (transcriptome) and microRNAs represent powerful tools for elucidating the pathogenesis of tumours, establishment of biomarkers and identifying possible drug targets. Several studies have been performed to date on the mRNA expression profiles of adrenocortical tumours. Some studies on the transcriptome of phaeochromocytomas and the microRNA expression patterns in adrenocortical and adrenomedullary tumours have also been recently reported. Transcriptome analysis in adrenocortical tumours has revealed markers useful for the differentiation of benign and malignant tumours (e.g. IGF2, topoisomerase 2A), markers for disease-free or total survival (DLG7, PINK1, BUB1) and several gene alterations relevant for tumourigenesis. In a recent meta-analysis of transcriptome and comparative genome hybridization studies including our own data, we have established three major pathways of adrenocortical cancer pathogenesis: i) damage of cell cycle, ii) retinoic acid signalling, iii) immune-complement changes. We have also established the damage of cell cycle as a pathway affected by microRNAs in adrenocortical cancer. Significantly differentially expressed microRNAs have been found both among normal adrenal cortex, benign and malignant adrenocortical tumours (miR-503, miR-511, miR-195 etc.), and in various sporadic benign, hereditary benign, sporadic recurrent (miR-1225-3p) and malignant phaeochromocytomas (miR-483-5p, miR-15a, miR-16 etc.). As the histological diagnosis of malignancy is difficult for adrenocortical tumours, but it is not feasible in phaeochromocytomas at all, these microRNA expression profiles may have major clinical relevance. Bioinformatic analysis of the potential mRNA targets of microRNAs has revealed the possible involvement of Notch-signaling in the pathogenesis of phaeochromocytoma recurrence. Despite these major achievements, there are many unclear issues yet and there are major differences in the studies reported that warrant further examinations.