MiR-34a and miR-483-5p are candidate serum biomarkers for adrenocortical tumors.
BACKGROUND
Nonfunctioning adrenal incidentalomas are common and many patients undergo adrenalectomy to exclude adrenocortical carcinoma (ACC). Recent studies have shown dysregulated microRNA (miRNA) expression in ACC. The objective of this study was to determine the feasibility and diagnostic accuracy of measuring serum miRNAs in patients with benign and malignant adrenocortical neoplasms.


METHODS
Five miRNAs were selected from miRNA profiling studies in ACC (miR-let-7d, -34a, -195, -214, and 483-5p). Total miRNA was extracted from serum samples in patients with malignant and benign adrenal neoplasms. miRNAs levels were measured by quantitative reverse transcript polymerase chain reaction and normalized to miR-16. To determine if miRNAs were secreted from ACC cells, we measured miRNA levels in culture.


RESULTS
Serum samples from 22 patients with cortical adenomas and 17 patients with ACC were analyzed, and all 5 miRNAs were detected. We found greater levels of miR-34a (P = .001) and miR-483-5p (P = .011) in patients with ACC. The area under the receiver operating characteristic curve was 0.81 for miR-34a and 0.74 for miR-438-5p. MiR-34a and miR-483-5p levels in ACC cells were greater in the supernatant at 48 hours compared with intracellular levels.


CONCLUSIONS
We show that dysregulated miRNAs in ACC are detectable in human serum samples. MiR-34a and miR-483-5p are candidate serum biomarkers for distinguishing between benign and malignant adrenocortical tumors.
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: pateldt@mail.nih.gov.
Dhaval
D
Patel
Myriem
M
Boufraqech
Meenu
M
Jain
Lisa
L
Zhang
Mei
M
He
Krisana
K
Gesuwan
Neelam
N
Gulati
Naris
N
Nilubol
Tito
T
Fojo
Electron
E
Kebebew
D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D000310:Adrenal Gland 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; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged
D014408:Biomarkers, Tumor; C552722:MIRN195 microRNA, human; C547397:MIRN214 microRNA, human; C522425:MIRN34 microRNA, human; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human