title: Analysis of circulating microRNAs in adrenocortical tumors.
abstract: Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumors (ACTs) is entirely different. Circulating microRNAs (miRNAs) are promising biomarker candidates of malignancy in several tumors; however, there are still numerous technical problems associated with their analysis. The objective of our study was to investigate circulating miRNAs in ACTs and to evaluate their potential applicability as biomarkers of malignancy. We have also addressed technical questions including the choice of profiling and reference gene used. A total of 25 preoperative plasma samples obtained from patients with ACAs and carcinomas were studied by microarray and quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197 and hsa-miR-1281) found as differentially expressed in plasma samples in our microarray screening could be validated by quantitative real-time PCR. In contrast, of the selected eight miRNAs reported in the literature as differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR-184, hsa-miR-210 and hsa-miR-483-5p) showed a statistically significant overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16 as a reference gene. Receiver operator characteristic analysis of data revealed that the combination of dCThsa-miR-210 - dCThsa-miR-181b and dCThsa-miR-100/dCThsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87 and 0.85, respectively). In conclusion, we have found significant differences in expression of circulating miRNAs between ACAs and carcinomas, but their diagnostic accuracy is not yet high enough for clinical application. Further studies on larger cohorts of patients are needed to assess the diagnostic and prognostic potential application of circulating miRNA markers.
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Diana Rita
authors: DR
authors: Szabó
authors: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors: Michaela
authors: M
authors: Luconi
authors: Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors: Peter M
authors: PM
authors: Szabó
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Miklós
authors: M
authors: Tóth
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Nikolette
authors: N
authors: Szücs
authors: 1st Department of Surgery, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: János
authors: J
authors: Horányi
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Zoltán
authors: Z
authors: Nagy
authors: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors: Massimo
authors: M
authors: Mannelli
authors: 1] Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary [2] 'Lendület-2013' Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
authors: Attila
authors: A
authors: Patócs
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Károly
authors: K
authors: Rácz
authors: 2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors: Peter
authors: P
authors: Igaz
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D018268:Adrenocortical Carcinoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000097:blood* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C544266:MIRN100 microRNA, human; C534424:MIRN184 microRNA, human; C543800:MIRN210 microRNA, human; C548912:MIRN483 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm