Elsevier

Surgery

Volume 154, Issue 6, December 2013, Pages 1224-1229
Surgery

American Association of Endocrine Surgeon
MiR-34a and miR-483-5p are candidate serum biomarkers for adrenocortical tumors

https://doi.org/10.1016/j.surg.2013.06.022Get rights and content

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.

Method

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.

Conclusion

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.

Section snippets

Serum samples

Fasting serum samples from patients with adrenocortical neoplasms were obtained the day of operation and stored at −80°C. Demographic, clinical, and pathologic information and tissue samples were collected under an institutional review board–approved protocol. Clinical characteristics of the study cohort are summarized in the Table. Tumors were classified as ACC if the Weiss criteria was ≥3. Tumors were classified as benign if the Weiss criteria was <3.

Serum miRNA extraction

MiRNA was extracted from serum using the

Results

Five miRNAs were measured in serum samples from patients with adrenocortical neoplasms. All 5 miRNAs were detected in serum and were normalized to miR-16, a miRNA that is present ubiquitously in serum.16 There were greater levels of miR-34a (P = .001) and miR-483-5p (P = .011) in patients with ACC (Fig 1). Mir-let-7d (P = .1975), miR-214 (P = .1370), and miR-195 (P = .9210) levels in serum were not different between patients with malignant and benign adrenocortical neoplasms (Fig 1). To

Discussion

To the authors’ knowledge, there have been no studies evaluating miRNAs levels in serum samples of patients with ACC. We showed that selected miRNAs that are dysregulated in adrenocortical neoplasms are detectable in human serum samples. Moreover, miR-34a and miR-483-5p are candidate serum biomarkers for distinguishing between benign and malignant adrenocortical tumors. Furthermore, we found that miR-34a and miR-483-5p were secreted by ACC cells. These miRNAs are dysregulated in ACC and could

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    A subset of these markers can be measured by non-invasive techniques. For instance somatic mutations may be detected in circulating tumor DNA [11,12], and specifically up-regulated miRNAs [13–15] may be detected in blood. Such approaches may help to detect these diseases.

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Supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

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