Endocrine Abstracts

Objective: To identify miRNAs predictors of poor prognosis in adrenocortical cancer.

Methods: Using microarrays, we evaluated the expression of 728 human miRNAs in six adenomas (ACAs) and twelve carcinomas (ACCs). The ACC group was composed of two subgroups A and B consisting of six recurrent (subgroup A) and six non-recurrent tumors (subgroup B). These two distinct subgroups have been characterized recently (de Reynies et al, 2009) on the basis of distinct gene expression profiles: comparison of global survival revealed a major difference in outcome in these two subtypes of ACC, with a very high rate of relapse and death within two years following surgery in the A subgroup.

Results: Twelve miRNAs were differentially expressed between ACCs and ACAs, 5 of which were down-regulated and 7 up-regulated in ACCs. The best discriminatory miRNAs between ACCs and ACAs were miR-195 and miR-335 which were down-regulated in ACCs. 29 miRNAs were differentially expressed between the two ACC subgroups A and B, with all discriminatory miRNAs more strongly expressed in A than in B carcinoma samples. Among them, miR-139-5p was the most powerful discriminatory miRNA between A and B subtypes with consistent up-regulation in recurrent carcinoma (A). Quantitative RT-PCR revealed that the levels of expression of miR-195 and miR-335 were similar in ACAs and normal adrenal cortex while strongly repressed in ACCs. Overexpression of miR-139-5p was confirmed in ACCs type A. These results were validated in a separate cohort of ten benign and twenty malignant samples (10 ACCs type A and 10 ACCs type B) using quantitative RT-PCR. Target prediction analysis revealed that predicted targets of these miRNAs are involved in biological processes which enhance tumor progression.

Conclusions: Our data suggest that adrenocortical cancer cells progressively switch from a high miR-195 and miR-335 status to a low miR-195 and miR-335 phenotype. miR-139-5P is a potential prognostic biomarker of recurrent ACCs.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.