MicroRNA expression profiling in adrenal myelolipoma

Abstract

Introduction: Adrenal myelolipoma (AML) is the second most common, and invariably benign primary adrenal neoplasm. Due to the variable proportion of fat and hematopoietic elements, and its often large size, it can cause differential diagnostic problems. Several reports confirmed the utility of microRNAs (miRNAs) in the diagnosis of tumors, but the miRNA expression in AML has not yet been investigated. Materials and methods: Next-generation sequencing (NGS) was performed on 30 formalin-fixed paraffin-embedded (FFPE) archived tissue [AML, adrenocortical adenoma (ACA) and adrenocortical carcinoma (ACC) 10 each] samples. Validation was performed by real-time RT-qPCR on a cohort containing 41 further FFPE samples (15 AML, 14 ACA and 12 ACC). Circulating miRNA counterparts of significantly differentially expressed tissue miRNAs were studied in altogether 33 plasma samples (ACA, ACC, AML 11 each). Results: By NGS, 256 significantly differentially expressed miRNAs were discovered, and 8 of these were chosen for validation. Significant overexpression of hsa-miR-451a, hsa-miR-486-5p, hsa-miR-363-3p and hsa-miR-150-5p was confirmed in AML relative to ACA and ACC. Hsa-miR-184, hsa-miR-483-5p and hsa-miR-183-5p were significantly overexpressed in ACC relative to ACA, but not to AML. Circulating hsa-miR-451a and hsa-miR-363-3p were significantly overexpressed in AML, whereas circulating hsa-miR-483-5p and hsa-miR-483-3p were only significantly overexpressed in ACC vs. ACA. Conclusions: We have found significantly differentially expressed miRNAs in AML and adrenocortical tumors. Circulating hsa-miR-451a might be a promising minimally invasive biomarker of AML. The lack of significantly different expression of hsa-miR-483-3p and hsa-miR-483-5p between AML and ACC might limit their applicability as diagnostic miRNA markers for ACC.