Endocrine Abstracts (2018) 56 OC8.1 | DOI: 10.1530/endoabs.56.OC8.1

Plasma microRNA expression in patients with Cushing's disease differs from ACTH-ectopic Cushing's syndrome

Zhanna Belaya1, Patimat Khandaeva1, Alexey Nikitin2, Alexander Solodovnikov3, Ivan Sitkin1, Tatjana Grebennikova1, Alexander Vorontsov1, Liudmila Rozhinskaya1, Galina Melnichenko1 & Ivan Dedov1

1The National Research Centre for Endocrinology, Russian Federation, Moscow, Russia; 2Federal Research and Clinical Center FMBA, Russian Federation, Moscow, Russia; 3Ural State Medical Academy, Ekaterinburg, Russian Federation, Moscow, Russia.

According to previous research microRNA (miR) are expressed differently in corticotropinoma and ACTH-secreting neuroendocrine tumors. MiR are released into circulation by several mechanisms and considered to be promising biomarkers.

Objective: To evaluate whether preselected miR are differently expressed in plasma samples of patients with ACTH-dependent Cushing’s syndrome (CS).

Materials and methods: The blood samples were collected in the morning from fasting patients with ACTH-dependent CS and stored at −80C. Twenty three miR, which were previously reported to be differently expressed in the ACTH-secreting tumors vs healthy tissue samples (has-miR-10-5p, has-miR-129-5p, has-miR-133a-5p; has-miR-141-3p; has-miR-143-3p; has-miR-145a-5p; has-miR-150-3p; has-miR-15a-5p; has-miR-16-5p; has-miR-145-5p; has-miR-146a-5p; has-miR-150-3p; has-miR-15a-5p; has-miR-185-3p; has-miR-191-5p; has-miR-203a-5p; has-miR-210-5p; has-miR-211-5p; has-miR-31-5p; has-miR-409-3p; has-miR-431-5p; has-miR-488-3p; has-miR-7g-5p) were quantified in plasma by qPCR (Applied Biosystems, USA).

Results: We enrolled 28 patients (4 men and 24 women) with Cushing’s disease (CD) with a mean age of 37 (95% CI 33–42); body mass index (BMI) 29.81 (27–32) kg/M2 and 13 patients with ACTH-ectopic syndrome (seven men and six women with a mean age of 43 years (33–52), BMI- 30.16 (28.82–31.50) kg/M2; and the healthy control group (2 men and 9 women) with a mean age of 39 years (33-44), BMI 28.21 (22.29-34.13) kg/M2. Patients with ACTH-depended CS were not different in 24hUFC or ACTH levels. Among measured miRs expressions, we found statistically significant differences in the expression of miR-16-5p (45.04 (95%CI 28.77–61.31) in CD vs 5.26 (2.65–7.87) in patients with ACTH-ectopic syndrome P<0.001; q=0.001); miR-145-5p (0.097 (0.027–0.167) in CD vs no expression in ACTH-ectopic CS P=0.008; q=0.087) and less evident in miR7g-5p (1.842 (1.283–2.400) in CD vs 0.847 (0.187–1.507) in ACTH-ectopic syndrome P=0.02; q=0.14). MiR- 16-5p was differently expressed in plasma samples from healthy subjects compared to both CD and ACTH-ectopic CS. MiR- 145-5p expression differed between ACTH-ectopic CS vs healthy subjects, but not CD vs healthy subjects; whereas miR- 7g-5p was differently expressed in CD vs healthy control, but did not differ from ACTH-ectopic CS vs healthy subjects

Conclusions: Plasma miR-expression differs in patients with CD and ACTH-ectopic CS. In particular miR-16-5p, miR—145-5p and miR—7g-5p are promising biomarkers for further research to differentiate ACTH-dependent CS.